Molecular and Cellular Biochemistry

, Volume 298, Issue 1–2, pp 1–40 | Cite as

Calcium signaling phenomena in heart diseases: a perspective

  • Sajal ChakrabortiEmail author
  • Sudip Das
  • Pulak Kar
  • Biswarup Ghosh
  • Krishna Samanta
  • Saurav Kolley
  • Samarendranath Ghosh
  • Soumitra Roy
  • Tapati Chakraborti
Review Paper


Ca2+ is a major intracellular messenger and nature has evolved multiple mechanisms to regulate free intracellular (Ca2+)i level in situ. The Ca2+ signal inducing contraction in cardiac muscle originates from two sources. Ca2+ enters the cell through voltage dependent Ca2+ channels. This Ca2+ binds to and activates Ca2+ release channels (ryanodine receptors) of the sarcoplasmic reticulum (SR) through a Ca2+ induced Ca2+ release (CICR) process. Entry of Ca2+ with each contraction requires an equal amount of Ca2+ extrusion within a single heartbeat to maintain Ca2+ homeostasis and to ensure relaxation. Cardiac Ca2+ extrusion mechanisms are mainly contributed by Na+/Ca2+ exchanger and ATP dependent Ca2+ pump (Ca2+-ATPase). These transport systems are important determinants of (Ca2+)i level and cardiac contractility. Altered intracellular Ca2+ handling importantly contributes to impaired contractility in heart failure. Chronic hyperactivity of the β-adrenergic signaling pathway results in PKA-hyperphosphorylation of the cardiac RyR/intracellular Ca2+ release channels. Numerous signaling molecules have been implicated in the development of hypertrophy and failure, including the β-adrenergic receptor, protein kinase C, Gq, and the down stream effectors such as mitogen activated protein kinases pathways, and the Ca2+ regulated phosphatase calcineurin. A number of signaling pathways have now been identified that may be key regulators of changes in myocardial structure and function in response to mutations in structural components of the cardiomyocytes. Myocardial structure and signal transduction are now merging into a common field of research that will lead to a more complete understanding of the molecular mechanisms that underlie heart diseases. Recent progress in molecular cardiology makes it possible to envision a new therapeutic approach to heart failure (HF), targeting key molecules involved in intracellular Ca2+ handling such as RyR, SERCA2a, and PLN. Controlling these molecular functions by different agents have been found to be beneficial in some experimental conditions.


Calcium Heart diseases Plasma membrane Sarco(endo)plasmic reticulum Signal transduction 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



Thanks are due to the ICMR (New Delhi); the LSRB (DRDO, Govt. of India), the CSIR (New Delhi), DBT (Govt. of India) and the UGC (New Delhi) for partly financing our research. Thanks are also due to Prof. N.K.Ganguly (Director General, ICMR, New Delhi), Dr. Vasasntha Muthuswami (Senior Deputy Director General, ICMR, New Delhi), Dr. Vijay Kumar (Deputy Director General, ICMR, New Delhi), Dr.W.Selvamurthy (Chief Controller, DRDO, Govt. of India), Prof. Kasturi Datta (SES, Jawaharlal Nehru University, New Delhi), Dr. A. Duggal (Director, DBT, Govt. of India), Dr. Mohan Mehra (Indomedix Inc., Houston, Texas, USA) and Dr. A. Mandal (University of Arizona, Tucson, USA) for their help and interest in our research. This article is dedicated to late Prof. Nityananda Saha who died on 2nd March, 2005 while continuing as the Vice Chancellor of the University of Kalyani.


  1. 1.
    Hasenfuss G, Pieske B (2002) Calcium cycling in congestive heart failure. J Mol Cell Cardiol 34:951–969PubMedGoogle Scholar
  2. 2.
    Meyer M, Schillinger W, Pieske B, Holubarsch C, Heilmann C, Posival H, Kuwajima G, Mikoshiba K, Just H, Hasenfuss G (1995) Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. Circulation 15:778–784 Google Scholar
  3. 3.
    Houser ST, Margulies KB (2003) Is depressed myocyte contractility centrally involved in heart failure? Circ Res 92:350–358PubMedGoogle Scholar
  4. 4.
    Fabiato A (1983) Calcium induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245:C1–C14PubMedGoogle Scholar
  5. 5.
    Bers DM (2002) Cardiac excitation–contraction coupling. Nature 415:198–205PubMedGoogle Scholar
  6. 6.
    Bers DM (2001) Excitation–contraction coupling and cardiac contractile force. Kluwer Academic Publishers Dordrecht The Netherlands pp.427Google Scholar
  7. 7.
    Leblanc N, Hume JR (1990) Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum. Science 248:372–376PubMedGoogle Scholar
  8. 8.
    Lipp P, Niggli E (1994) Sodium current-induced calcium signals in isolated guinea-pig ventricular myocytes. J Physiol 474:439–446PubMedGoogle Scholar
  9. 9.
    Philipson KD, Nicoll DA (2000) Sodium-calcium exchange: a molecular perspective. Ann Rev Physiol 62:111–133Google Scholar
  10. 10.
    Molkentin JD, Dorn GW 2nd (2001) Cytosolic signaling pathways that regulate cardiac hypertrophy. Ann Rev Physiol 63:391–426Google Scholar
  11. 11.
    Dalhoff B, Pennert K, Hansson L (1992) Reversal of left ventricular hypertrophy in hypertensive patients: a meta analysis of 109 treatment studies. Am J Hyperens 5:95–110Google Scholar
  12. 12.
    Susie D, Nunez E, Frohlich ED (1995) Reversal of hypertrophy: an active biologic process. Curr Opin Cardiol 10:466–472Google Scholar
  13. 13.
    Martonosi AN, Pikula S (2003) The network of calcium regulation in muscle. Acta Biochim Pol 50:1–30PubMedGoogle Scholar
  14. 14.
    Striessnig J (1999) Pharmacology, structure and function of cardiac L-type Ca2+ channels. Cell Physiol Biochem 9:242–269PubMedGoogle Scholar
  15. 15.
    Lacinova L (2005) Voltage-dependent calcium channels. Gen Physiol Biophys Suppl 1:1–78Google Scholar
  16. 16.
    Meir A (2005) Voltage dependent Ca2+ (Cav) channels. Modulator (alomone labs, Jerusalem, Israel) 20(fall):2–6Google Scholar
  17. 17.
    Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT (2004) Cav1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119:19–31PubMedGoogle Scholar
  18. 18.
    Zhainazarov AB (2003) Ca2+-activated nonselective cation channels in rat neonatal atrial myocytes. J Membr Biol 193:91–98Google Scholar
  19. 19.
    Isenberg G (1993) Nonselective cation channels in cardiac and smooth muscle cells. EXS 66:247–260PubMedGoogle Scholar
  20. 20.
    Verkerk AO, Veldkamp MW, Bouman LN, van Ginnenken AC (2000) Calcium-activated (Cl-) current contributes to delayed after depolarizations in single Purkinje and ventricular myocytes. Circulation 101:2639–2644PubMedGoogle Scholar
  21. 21.
    Yee R, Brown KK, Bolster DE, Strauss HC (1988) Relationship between ionic perturbations and electrophysiologic changes in a canine Purkinje fibre model of ischemia and reperfusion. J Clin Invest 82:225–233PubMedGoogle Scholar
  22. 22.
    Tarr M, Arriaga E, Goertz KK, Valenzeno DP (1994) Properties of cardiac I(leak) induced by photosensitizer-generated reactive oxygen. Free Radic Biol Med 16:477–484PubMedGoogle Scholar
  23. 23.
    Chakraborti S, Gurtner GH, Michael JR (1989) Oxidant-mediated activation of phospholipase A2 in pulmonary endothelium. Am J Physiol 257:L430–L437PubMedGoogle Scholar
  24. 24.
    Strehler EE, Treiman M (2004) Calcium pumps of plasma membrane and cell interior. Curr Mol Med 4:323–335PubMedGoogle Scholar
  25. 25.
    Lehotsky J, Kaplan P, Murin R, Raeymaekers L (2002) The role of plasma membrane Ca2+ pump (PMCAs) in pathologies of mammalian cells. Front Biosci 7:d53–d84PubMedGoogle Scholar
  26. 26.
    Ganz MB, Boyarsky G, Sterzel RB, Boron WF (1989) Arginine vasopressin enhances (pH)i regulation in the presence of HCO3- by stimulating three acid-base transport systems. Nature (London) 337:648–651Google Scholar
  27. 27.
    Karmazyn M, Gan XT, Humphreys RA, Yoshida H, Kusumoto K (1999) The myocardial Na+/H+ exchange: structure, regulation, and its role in heart disease. Circ Res 85:777–786PubMedGoogle Scholar
  28. 28.
    Guerini D, Pan B, Carafoli E (2003) Expression, purification, and characterization of isoform 1 of the plasma membrane Ca2+ pump: focus on calpain sensitivity. J Biol Chem 278:38141–38148PubMedGoogle Scholar
  29. 29.
    Chakraborti T, Das S, Mandal M, Mandal A, Chakraborti S (2002) Role of Ca2+-dependent metalloprotease-2 in stimulating Ca2+ ATPase activity under peroxynitrite treatment in bovine pulmonary artery smooth muscle membrane. IUBMB Life 53:167–173PubMedGoogle Scholar
  30. 30.
    Inoue R, Okada T, Onoue H, Shimizu S, Naitoh S, Mori Y (2001) The transient receptor potential protein homologue TRP6 is the essential component of vascular α1-adrenoceptor-activated Ca2+ permeable cation channel. Circ Res 88:325–332PubMedGoogle Scholar
  31. 31.
    Dhalla NS, Temah RM, Netticadan T (2000) Role of oxidative stress in cardiovascular disease. J Hypertens 18:655–673PubMedGoogle Scholar
  32. 32.
    Mishra S, Sabbah HN, Jaain JC, Gupta RC (2003) Reduced Ca2+/calmodulin dependent protein kinase activity and expression in LV myocardium of dogs with heart faailure. Am J Physiol 284:H876–H883Google Scholar
  33. 33.
    Neyses L, Reinlib L, Carafoli E (1985) Phosphorylation of the Ca2+ pumping ATPase of heart sarcolemma and erythrocyte plasma membnrane by the cAMP-dependent protein kinase. J Biol Chem 260:10283–10287PubMedGoogle Scholar
  34. 34.
    James PH, Preschey M, Vohrerr T, Penninston JT, Carafoli E (1998) Primary structure of cAMP dependent phosphorylation site of the plasma membrane calcium pump. Biochemistry 28:4253–4258Google Scholar
  35. 35.
    Khan I, Grover AK (1991) Expression of cyclic-nucleotide-sensitive and -insensitive isoforms of plasma membrane Ca2+ pump in smooth muscle and other tissues. Biochem J 277:345–349PubMedGoogle Scholar
  36. 36.
    Tao J, Johansson JS, Haynes DH (1992) Protein kinase C stimulate dense tubular Ca2+ uptake in the intact human platelet by increasing the Vm of the Ca2+-ATPase pump: stimulation by phorbol ester, inhibition by calphostin C. Biochim Biophys Acta 1107:213–222PubMedGoogle Scholar
  37. 37.
    Wang KK, Wright LC, Machan CL, Allen BG, Conigrave AD, Roufogalis BD (1991) Protein kinase C phosphorylates the carboxyl terminus of the plasma membrane Ca2+-ATPase from human erythrocytes. J Biol Chem 266:9078–9085PubMedGoogle Scholar
  38. 38.
    Enyedi A, Elwess NL, Filoteo AG, Verma AK, Paszty K, Penniston JT (1997) Protein kinase C phosphorylates the “a” forms of the plasma membrane Ca2+ pump isoforms 2 and 3 and prevents binding of calmodulin. J Biol Chem 272:27525–27528PubMedGoogle Scholar
  39. 39.
    Verma AK, Paszty K, Frloteo AG, Penninston JT, Enyedi A (1999) Protein kinase C phosphorylates plasma membrane Ca2+ pump isoform 4a at its calmodulin binding domain. J Biol Chem 274:527–531PubMedGoogle Scholar
  40. 40.
    Enyedi A, Verma AK, Filoteo AG, Penninston JT (1996) Protein kinase C activates the plasma membrane Ca2+ pump isoform 4b by phosphorylation of an inhibitory region downstream of the calmodulin-binding domain. J Biol Chem 271:32461–32467PubMedGoogle Scholar
  41. 41.
    Zylinska L, Soszynski M (2000) Plasma membrane Ca2+-ATPase in excitable and nonexcitable cells. Acta Biochim Pol 47:529–539PubMedGoogle Scholar
  42. 42.
    Sugden PH, Bogoyevitch MA (1995) Intracellular signaling through protein kinases in the heart. Cardiovasc Res 30:478–492PubMedGoogle Scholar
  43. 43.
    Terentyev D, Viatchenko-Karpinski S, Gyorke I, Terentyeva R, Gyorke S (2003) Protein phosphatases decrease sarcoplasmic reticulum calcium content by stimulating calcium release in cardiac myocytes. J Physiol 552:109–118PubMedGoogle Scholar
  44. 44.
    Levitsky J, Gurell D, Frishman WH (1998) Sodium ion/hydrogen ion inhibition: a new pharmacologic appproach to myocardial ischemia and reperfusion injury. J Clin Pharmacol 38:887–897PubMedGoogle Scholar
  45. 45.
    Gan XT, Chakraborti S, Karmazyn M (1999) Modulation of Na+/H+ exchange isoform 1 mRNA expression in isolated rat hearts. Am J Physiol 277:H993–H998PubMedGoogle Scholar
  46. 46.
    Karmazyn M, Sawyer M, Fliegel L (2005) Na+/H+ exchanger: a target for cardiac therapeutic intervention. Curr Drug Targets Cardiovasc Haematol Disord 5:323–335PubMedGoogle Scholar
  47. 47.
    Rasmussen H, Rasmussen JE (1990) Calcium as intracellular messanger from simplicity to complexity. In: Horecker BL, Chock PB, Stadtman ER, Levitzki A (eds), Current topics in␣cellular regulation, vol. 31. Academic Press, New York, pp␣1–109Google Scholar
  48. 48.
    Colbran RJ, Schworer CM, Hashimoto Y, Fong YL, Rich DP, Smith MK, Soderling TR (1989) Calcium/calmodulin-dependent protein kinase II. Biochem J 258:313–325PubMedGoogle Scholar
  49. 49.
    Stagg MA, Terracciano CM (2005) Less Na+/H+-exchanger to treat heart failure: a simple solution for a complex problem? Cardiovasc Res 65:10–12PubMedGoogle Scholar
  50. 50.
    Takimoto E, Yao A, Toko H, Takano H, Shimoyama M, Sonoda M, Wakimoto K, Takahashi T, Akazawa H, Mizukami M, Nagai T, Nagai R, Komuro I (2002) Sodium calcium exchanger plays a key role in alteration of cardiac function in response to pressure overload. FASEB J 16:373–378PubMedGoogle Scholar
  51. 51.
    Rahamimoff H (1990) Na+/Ca2+ exchanger: the elusive protein. Curr Top Cell Regul 31:241–271PubMedGoogle Scholar
  52. 52.
    Philipson KD (1999) Sodium–Calcium exchange. In: E Carafoli and CB Klee (eds) Calcium as a cellular regulator. Oxford University Press, New York, pp 279–294 Google Scholar
  53. 53.
    Akabas MH (2004) Na+/Ca2+ exchange inhibitors: potential drugs to mitigate the severity of ischemic injury. Mol Pharmacol 66:8–10PubMedGoogle Scholar
  54. 54.
    Saini HK, Arneja AS, Dhalla NS (2004) Role of cholesterol in cardiovascular dysfunction. Can J Cardiol 20:333–346PubMedGoogle Scholar
  55. 55.
    Jeremy RW, McCarron H (2000) Effect of hypercholesterolemia on Ca2+ dependent K+ channel-mediated vasodilation in vivo. Am J Physiol Heart Circ Physiol 279:H1600–H1608PubMedGoogle Scholar
  56. 56.
    de Zwart LL, Meerman JH, Commandeur JN, Vermeulen NP (1999) Biomarkers of free radical damage application in experimental animals and in humans. Free Radic Biol Med 26:202–206PubMedGoogle Scholar
  57. 57.
    Mishra OP, Delivoria-Papadopoulos M (1999) Cellular mechanisms of hypoxic injury in the developing brain. Brain Res Bull 48:233–238PubMedGoogle Scholar
  58. 58.
    Kourie JI (1998) Interaction of reactive oxygen species with ion transport mechanisms. Am J Physiol 275:C1–C24PubMedGoogle Scholar
  59. 59.
    Racay P, Kaplan P, Mezesova V, Lehotsky J (1997) Lipid peroxidation both inhibits Ca2+-ATPase and increases Ca2+ permeability of endoplasmic reticulum membrane. Biochem Mol Biol Int 41:647–655PubMedGoogle Scholar
  60. 60.
    Squier TC, Bigelow DJ (2000) Protein oxidation and age-dependent alteration in calcium homeostasis. Front Biosci 5:d504–d526PubMedGoogle Scholar
  61. 61.
    Laporte R, Hui A, Laher I (2004) Pharmacological modulation of sarcoplasmic reticulum function in smooth muscle. Pharmacol Rev 56:439–513PubMedGoogle Scholar
  62. 62.
    East JM (2000) Sarco(endo)plasmic reticulum calcium pumps: recent advances in our understanding of structure/function and biology. Mol Membr Biol 17:189–200PubMedGoogle Scholar
  63. 63.
    Castilho RF, Carvalho-Alves PC, Vercesi AE, Ferreira ST (1996) Oxidative damage to sarcoplasmic reticulum Ca2+-pump induced by Fe2+/H2O2/ascorbate is not mediated by lipid peroxidation or thiol oxidation and leads to protein fragmentation. Mol Cell Biochem 159:105–114PubMedGoogle Scholar
  64. 64.
    Moreau VH, Castilho RF, Ferreira ST, Carvalho-Alves PC (1998) Oxidative damage to sarcoplasmic reticulum Ca2+-ATPase at submicromolar iron concentrations: evidence for metal-catalyzed oxidation. Free Radic Biol Med 25:554–560PubMedGoogle Scholar
  65. 65.
    Schuessler H, Schilling K (1984) Oxygen effect in the radiolysis of proteins. Part 2. Bovine serum albumin. Int J Radiat Biol Relat Stud Phys Chem Med 45:267–281PubMedGoogle Scholar
  66. 66.
    Davies KJ, Delsignore ME (1987) Protein damage and degradation by oxygen radicals. III. Modification of secondary and tertiary structure. J Biol Chem 262:9908–9913PubMedGoogle Scholar
  67. 67.
    Uchida K, Kato Y, Kawakishi S (1990) A novel mechanism for oxidative cleavage of prolyl peptides induced by the hydroxyl radical. Biochem Biophys Res Commun 169:265–271PubMedGoogle Scholar
  68. 68.
    Stadtman ER (1993) Oxidation of free amino acids and aminoacid residues in proteins by radiolysis and by metal-catalysed reactions. Annu Rev Biochem 62:797–821PubMedGoogle Scholar
  69. 69.
    Hasenfuss G (1998) Alterations of calcium-regulatory proteins in heart failure. Cardiovasc Res 37:279–289PubMedGoogle Scholar
  70. 70.
    Williams RJP (1999) Calcium: the developing role of its chemistry in biological evolution In: Carafoli E, Klee CB (eds) Calcium as a cellular regulatory. Oxford University Press, USA, pp 3–27Google Scholar
  71. 71.
    Bailey K (1942) Myosin and adenosinetriphosphatase. Biochem J 36:121–139PubMedGoogle Scholar
  72. 72.
    Carafoli E (2002) Calcium signaling: a tale of all seasons. Proc Natl Acad Sci (USA) 99:1115–1122Google Scholar
  73. 73.
    Garcia ML, Murray KD, Garcia VB, Strehler EE, Isackson PJ (1997) Seizure-induced alterations of plasma membrane Ca2+-ATPase isoforms 1,2 and 3 mRNA and protein in rat hippocampus. Brain Res Mol Brain Res 45:230–238PubMedGoogle Scholar
  74. 74.
    Schwinger RH, Munch G, Bolck B, Karczewski P, Krause EG, Erdmann E (1999) Reduced Ca2+-sensitivity of SERCA2a in failing human myocardium due to reduced serin-16 phospholamban phosphorylation. J Mol Cell Cardiol 31:479–491PubMedGoogle Scholar
  75. 75.
    Sande JB, Sjaastad I, Hoen IB, Bokenes J, Tonnessen T, Holt E, Lunde PK, Christensen G (2002) Reduced level of serine16 phosphorylated phospholamban in the failing rat myocardium: a major contributor to reduced SERCA2 activity. Cardiovasc Res 53:382–391PubMedGoogle Scholar
  76. 76.
    Yano M, Kobayashi S, Kohno M, Doi M, Tokuhisa T, Okuda S, Suetsugu M, Hisaoka T, Obayashi M, Ohkusa T, Kohno M, Matsuzaki M (2003) FKBP12.6-mediated stabilization of calcium-release channel (ryanodine receptor) as a novel therapeutic strategy against heart failure. Circulation 107:477–484PubMedGoogle Scholar
  77. 77.
    Bohn M, Reiger B, Schwinger RH, Erdman E (1994) cAMP concentrations, cAMPP dependent protein kinase activity and phospholamban in non-failing myocardium. Cardiovasc Res 28:1713–1719Google Scholar
  78. 78.
    Netticadan T, Temsah RM, Kawabata K, Dhalla NS (2000) Sarcoplasmic reticulum Ca2+/calmodulin dependent protein kinase is altered in heart failure. Circ Res 86:596–605PubMedGoogle Scholar
  79. 79.
    Frank KF, Bolck B, Erdmann EE, Schwinger RH (2003) Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation. Cardiovasc Res 57:20–27PubMedGoogle Scholar
  80. 80.
    Yano M, Ikeda Y, Matsuzaki M (2005) Altered intracellular Ca2+ handling in heart failure. J Clin Invest 115:556–564PubMedGoogle Scholar
  81. 81.
    Francis GS (2001) Pathophysiology of chronic heart failure. Am J Med 110:S37–S46Google Scholar
  82. 82.
    Braunwald E, Bristow MR (2000) Congestive heart failure: fifty years of progress. Circulation 102:IV14–IV23PubMedGoogle Scholar
  83. 83.
    Braz JC, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, Kimball TF, Lorenz JN, Nairn AC, Liggett SB, Bodi I, Wang S, Schwartz A, Lakatta EG, DePaoli-Roach AA, Robbins J, Hewett TE, Bibb JA, Westfall MV, Kranias EG, Molkentin JD (2004) PKCα regulates cardiac contractility and propensity toward heart failure. Nat Med 10:248–254PubMedGoogle Scholar
  84. 84.
    Schoneich C, Viner RI, Ferrington DA, Bigelow DJ (1999) Age-related chemical modification of the skeletal muscle sarcoplasmic reticulum Ca2+-ATPase of the rat. Mech Ageing Dev 107:221–231PubMedGoogle Scholar
  85. 85.
    Klebl BM, Ayoub AT, Pette D (1998) Protein oxidation, tyrosine nitration and inactivation of sarcoplasmic reticulum Ca2+-ATPase in low-frequency stimulated rabbit muscle. FEBS Lett 422:381–384PubMedGoogle Scholar
  86. 86.
    Kargacin ME, Kargacin GJ (1995) Direct measurement of Ca2+ uptake and release by the sarcoplasmic reticulum of saponin permeabilized isolated smooth muscle cells. J Gen Physiol 106:467–484PubMedGoogle Scholar
  87. 87.
    Iwamoto T, Wakabayashi S, Shigekawa M (1995) Growth factor-induced phosphorylation and activation of aortic smooth muscle Na+/Ca2+ exchanger. J Biol Chem 270:8996–9001PubMedGoogle Scholar
  88. 88.
    Dixon IMC, Kaneko M, Hata T, Panagia V, Dhalla NS (1990) Alterations in cardiac membrane calcium transport during oxidative stress. Mol Cell Biochem 99:125–133PubMedGoogle Scholar
  89. 89.
    Hata T, Kaneko M, Beamish E, Dhalla NS (1991) Influence of oxygen free radicals on heart sarcolemmal Na+/Ca2+ exchange. Coronary Artery Dis 2:397–407Google Scholar
  90. 90.
    Reeves JP, Bailey CA, Hales CC (1986) Redox modification of sodium–calcium exchange activity in cardiac sarcolemmal vesicles. J Biol Chem 561:4948–4955Google Scholar
  91. 91.
    Shi ZQ, Davison AJ, Tibbits GF (1989) Effects of active oxygen generated by DTT/Fe2+ on cardiac Na+/Ca2+ exchange and membrane permeability to Ca2+. J Mol Cell Cardiol 21:1009–1016PubMedGoogle Scholar
  92. 92.
    DiPolo R, Beauge L (1993) In squid axons the (Ca2+)i regulatory site of the Na+/Ca2+ exchanger is drastically modified by sulfhydryl blocking agents. Evidences that intracellular (Ca2+)i regulatory and transport sites are different. Biochim Biophys Acta 1145:75–84Google Scholar
  93. 93.
    Coetzee WA, Ichikawa H, Hearse DJ (1994) Oxidant stress inhibits Na+-Ca2+-exchange current in cardiac myocytes: mediation by sulfhydryl groups? Am J Physiol 266:H909–H919PubMedGoogle Scholar
  94. 94.
    Chemnitius JM, Sasaki Y, Burger W, Bing RJ (1985) The effect of ischemia and reperfusion on sarcolemmal function in perfused canine hearts. J Mol Cell Cardiol 17:1139–1150PubMedGoogle Scholar
  95. 95.
    Lamers JM, Post JA, Verkleij AJ, Ten Cate FJ, van der Giessen WJ, Verdouw PD (1987) Loss of functional and structural integrity of the sarcolemma: an early indicator of irreversible injury of myocardium?. Biomed Biochim Acta 46:S517–S521PubMedGoogle Scholar
  96. 96.
    Samouilidou EC, Karli JN, Levis GM, Darsinos J (1998) The sarcolemmal Ca2+-ATPase of ischemic-reperfused myocardium: protective effect of hypocalcemia on calmodulin stimulated activity. Life Sci 62:29–36PubMedGoogle Scholar
  97. 97.
    Guerini D, Carafoli E (1999) The calcium pumps. In: Carafoli E, Klee CB (Eds) Calcium as a cellular regulator. Oxford University Press, New York, pp 249–278Google Scholar
  98. 98.
    Gibson A, McFadzean I, Wallace P, Wayman CP (1998) Capacitative Ca2+ entry and the regulation of smooth muscle tone. Trends Pharmacol Sci 19:266–269PubMedGoogle Scholar
  99. 99.
    Bassani JW, Bassani RA, Bers DM (1994) Relaxation in rabbit and rat cardiac cells: species dependent difference in cellular mechanisms. J Physiol 476:279–293PubMedGoogle Scholar
  100. 100.
    Fill M, Zahradnikova A, Villalba-Galea CA, Zahradnik I, Escobar AL, Gyorke S (2000) Ryanodine receptor adaptation. J Gen Physiol 116:873–882PubMedGoogle Scholar
  101. 101.
    Sitsapesan R, Williams AJ (2000) Do inactivation mechanisms rather than adaptation hold the key to understanding ryanodine receptor channel gating? J Gen Physiol 116:867–872PubMedGoogle Scholar
  102. 102.
    Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers and permeability transitions. Physiol Rev 79:1127–1155PubMedGoogle Scholar
  103. 103.
    Mackenzie L, Roderick HL, Proven A, Conway SJ, Bootman MD (2004) Inositol 1,4,5-trisphosphate receptors in the heart. Biol Res 37:553–557PubMedCrossRefGoogle Scholar
  104. 104.
    Pessah IN, Kim KH, Feng W (2002) Redox sensing properties of the ryanodine receptor complex. Front Biosci 7:a72–a79PubMedGoogle Scholar
  105. 105.
    Zima AV, Copello JA, Blatter LA (2004) Effects of cytosolic NADH/NAD+ levels on sarcoplasmic reticulum Ca2+ release in permeabilized rat ventricular myocytes. J Physiol 555:727–741PubMedGoogle Scholar
  106. 106.
    Suzuki YJ, Ford GD (1999) Redox regulation of signal transduction in cardiac and smooth muscle. J Mol Cell Cardiol 31:345–353PubMedGoogle Scholar
  107. 107.
    Enger KR, Dulhunty AF (1999) Cardiac ryanodine receptor activity is altered by oxidizing reagents in either the luminal or cytosolic solution. J Membr Biol 167:205–214Google Scholar
  108. 108.
    Masion PB, Feron O, Dessy C, Balligand JL (2003) Nitric oxide and cardiac function: ten years after, and continuing. Circ Res 934:388–398Google Scholar
  109. 109.
    Xu L, Eu JP, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234–237PubMedGoogle Scholar
  110. 110.
    Xu KY, Huso DL, Dawson T, Bredt DS, Becjker LC (1999) NO synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci (USA) 96:657–662Google Scholar
  111. 111.
    Sears CE, Bryant SM, Ashley EA, Lygate CA, Rakovic S, Wallis HL, Neubauer S, Terrar DA, Casadei B (2003) Cardiac neuronal nitric oxide synthase isoform regulates myocardial contraction and calcium handling. Circ Res 92:e52–e59PubMedGoogle Scholar
  112. 112.
    Khan SA, Skaf MW, Harrison RW, Lee K, Minhas KM, Kumar A, Fradley M, Shoukas AA, Berkowitz DE, Hare JM (2003) Nitric oxide regulation of myocardial contractility and calcium cycling: independent impact of neuronal and endothelial nitic oxide synthase. Circ Res 92:1322–1329PubMedGoogle Scholar
  113. 113.
    Ashley EA, Sears CE, Bryant SM, Watkins HC, Casadei B (2002) Cardiac nitric oxide synthase I regulates basal and β-adrenergic contractility in murine ventricular myocytes. Circulation 105:3011–3016PubMedGoogle Scholar
  114. 114.
    Hidalgo C, Donoso P, Carrasco MA (2005) The ryanodine receptors Ca2+ release channels: cellular redox sensors? IUBMB Life 57:315–322PubMedGoogle Scholar
  115. 115.
    Wagenknecht T, Grassucci R, Frank J, Saito A, Inui M, Fleischer S (1989) Three-dimensional architecture of the calcium channel/foot structure of sarcoplasmic reticulum. Nature 338:167–170PubMedGoogle Scholar
  116. 116.
    Bers DM (2004) Macromolecular complexes regulating cardiac ryanodine receptor function. J Mol Cell Cardiol 37:417–429PubMedGoogle Scholar
  117. 117.
    Marks AR (2002) Ryanodine receptors, FKBP12, and heart failure. Frot Biosci 7:d970–d977Google Scholar
  118. 118.
    Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR (2000) PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 101:365–376PubMedGoogle Scholar
  119. 119.
    Marks AR, Reiken S, Marx SO (2002) Progression of heart failure: is protein kinase A hyperphosphorylation of the ryanodine receptor a contributing factor? Circulation 105:272–275PubMedGoogle Scholar
  120. 120.
    Lehnart SE, Wehrens XH, Marks AR (2004) Calstabin deficiency, ryanodine receptors, and sudden cardiac death. Biochem. Biophys Res Commun 322:1267–1279PubMedGoogle Scholar
  121. 121.
    Wehrens XH, Marks AR (2003) Altered function and regulation of cardiac receptors in cardiac disease. Trends Biochem Sci 28:671–678PubMedGoogle Scholar
  122. 122.
    Marx SO, Gaburjakova J, Gaburjakova M, Henrikson C, Ondrias K, Marks AR (2001) Coupled gating between cardiac calcium release channels (ryanodine receptors). Circ Res 88:1151–1158PubMedGoogle Scholar
  123. 123.
    Shanon TR, Pogwizd SM, Bers DM (2003) Elevated sarcoplasmic reticulum Ca2+ leak in intact ventricular myocytes from rabbits in heart failure. Circ Res 93:592–594Google Scholar
  124. 124.
    Yano M, Ono K, Ohkusa T, Suetsugu M, Kohno M, Hisaoka T, Kobayashi S, Hisamatsu Y, Yamamoto T, Kohno M, Noguchi N, Takasawa S, Okamoto H, Matsuzaki M (2000) Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca2+ leak through ryanodine receptor in heart failure. Circulation 102:2131–2136PubMedGoogle Scholar
  125. 125.
    Callewaert G, Cleemann L, Morad M (1988) Epinephrine enhances Ca2+ current-regulated Ca2+ release and Ca2+ reuptake in rat ventricular myocytes. Proc Natl Acad Sci (USA) 85:2009–2013Google Scholar
  126. 126.
    Kranias EG, Garvey JL, Srivastava RD, Solaro RJ (1985) Phosphorylation and functional modifications of sarcoplasmic reticulum and myofibrils in isolated rabbit hearts stimulated with isoprenaline. Biochem J 226:113–121PubMedGoogle Scholar
  127. 127.
    Reiken S, Wehrens XH, Vest JA, Barbone A, Klotz S, Mancini D, Burkhoff D, Marks AR (2003) β-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure. Circulation 107:2459–2466PubMedGoogle Scholar
  128. 128.
    Frank KF, Bolck B, Brixius K, Kranias EG, Schwinger RH (2002) Modulation of SERCA: implications for the failing human heart. Basic Res Cardiol 97(Suppl 1):I72–I78PubMedGoogle Scholar
  129. 129.
    Zaccolo M, Pozzan T (2002) Discrete mimicrodomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes. Science 295:1711–1715Google Scholar
  130. 130.
    Su Z, Sugishita K, Li F, Ritter M, Barry WH (2003) Effects of FK506 on (Ca2+)i differ in mouse and rabbit ventricular myocytes. J Pharmacol Exp Ther 304:334–341PubMedGoogle Scholar
  131. 131.
    Barry WH, Gilbert EM (2003) How do β-blockers improve ventricular function in patients with congestive heart failure? Circulation 107:2395–2397PubMedGoogle Scholar
  132. 132.
    Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signaling: dynamics, homeostasis and remodeling. Nat Rev Mol Cell Biol 4:517–529PubMedGoogle Scholar
  133. 133.
    Muller FU, Kirchhefer U, Begrow F, Reinke U, Neumann J, Schmitz W (2002) Junctional sarcoplasmic reticulum transmembrane proteins in the heart. Basic Res Cardiol 97:152–155CrossRefGoogle Scholar
  134. 134.
    Zhang L, Iley J, Schmeisser G, Kobayashi YM, Jones LR (1997) Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane. J Biol Chem 272:23389–23397PubMedGoogle Scholar
  135. 135.
    Churchill GC, Okada Y, Thomas JM, Genazzani AA, Patel S, Galione A (2002) NAADP mobilizes Ca2+ from reserve granules, lysosome-related organelles, in sea urchin eggs. Cell 111:703–708PubMedGoogle Scholar
  136. 136.
    Hua SY, Tokimasa T, Takasawa S, Furuya Y, Nohmi M, Okamoto H, Kuba K (1994) Cyclic ADP-ribose modulates Ca2+ release channels for activation by physiological Ca2+ entry in bullfrog sympathetic neurons. Neuron 12:1073–1079PubMedGoogle Scholar
  137. 137.
    Cui Y, Galione A, Terrar DA (1999) Effects of photoreleased cADP ribose on calcium transients and calcium sparks in myocytes isolated from guinea pig and rat ventricle. Biochem J 342:269–273PubMedGoogle Scholar
  138. 138.
    Rakovic S, Cui Y, Iino S, Galione A, Ashamu GA, Potter BV, Terrar DA (1999) An antagonist of cADP-ribose inhibits arrhythmogenic oscillations of intracellular Ca2+ in heart cells. J Biol Chem 274:17820–17827PubMedGoogle Scholar
  139. 139.
    Casteels R, Droogmans G (1981) Exchange characteristics of the noradrenaline-sensitive calcium store in vascular smooth muscle cells or rabbit ear artery. J Physiol (London) 317:263–279Google Scholar
  140. 140.
    Parekh AB, Putney JW Jr (2005) Store-operated calcium channels. Physiol Rev 85:757–810PubMedGoogle Scholar
  141. 141.
    Putney JW Jr (2005) Capacitative calcium entry: sensing the calcium stores. J Cell Biol 169:381–382PubMedGoogle Scholar
  142. 142.
    Putney JW Jr (1993) Excitement about calcium signaling in inexcitable cells. Science 262:676–678PubMedGoogle Scholar
  143. 143.
    Berridge MJ (1995) Capacitative calcium entry. Biochem J 312:1–11PubMedGoogle Scholar
  144. 144.
    Putney JW Jr, Bird GS (1993) The signal for capacitative calcium entry. Cell 75:199–201PubMedGoogle Scholar
  145. 145.
    Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169:435–445PubMedGoogle Scholar
  146. 146.
    Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15:1235–1241PubMedGoogle Scholar
  147. 147.
    Putney JW Jr (1977) Muscarinic, α-adrenergic and peptide receptors regulate the same calcium influx sites in the parotid gland. J Physiol (London) 268:139–149Google Scholar
  148. 148.
    Barritt GJ (1999) Receptor activated Ca2+ inflow in animal cells: a variety of pathways tailored to meet different intracellular Ca2+ signaling requirements. Biochem J 337:153–169PubMedGoogle Scholar
  149. 149.
    Putney JW Jr (1997) Capacitative calcium entry. In: Landes Biomedical Publishing, Ausin, Texas. 210 ppGoogle Scholar
  150. 150.
    Ramsey IS, Delling M, Clapham DE (2006) An introduction to TRP channels Annu Rev Physiol 68:619–647PubMedGoogle Scholar
  151. 151.
    Riccio A, Mattei C, Kelsell RE, Medhurst AD, Calver AR, Randall AD, Davis JB, Benham CD, Pangalos MN (2002) Cloning and functional expression of human short TRP7, a candidate protein for store-operated Ca2+ influx. J Biol Chem 277:12302–12309PubMedGoogle Scholar
  152. 152.
    Hofmann T, Schaefer M, Schultz G, Gudermann T (2000) Cloning, expression and subcellular localization of two novel splice variants of mouse transient receptor potential channel 2. Biochem J 351:115–122PubMedGoogle Scholar
  153. 153.
    Ohki G, Miyoshi T, Murata M, Ishibashi K, Imai M, Suzuki M (2000) A calcium-activated cation current by an alternatively spliced form of TRP3 in the heart. J Biol Chem 275:39055–39060PubMedGoogle Scholar
  154. 154.
    Sweeney M, Yu Y, Platoshyn O, Zhang S, McDaniel SS, Yuan JX (2002) Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation. Am J Physiol 283:L144–L155Google Scholar
  155. 155.
    Welsh DG, Morielli AD, Nelson MT, Brayden JE (2002) Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res 90:248–250PubMedGoogle Scholar
  156. 156.
    Clementi E, Meldolesi J (1997) The cross-talk between nitric oxide and Ca2+: a story with a complex past and a promising future. Trends Pharmacol Sci 18:266–269PubMedGoogle Scholar
  157. 157.
    Wayman CP, McFadzean I, Gibson A, Tucker JF (1996) Inhibition by sodium nitroprusside of a calcium store depletion-activated non-selective cation current in smooth muscle cells of the mouse anococcygeus. Br J Pharmacol 118:2001–2008PubMedGoogle Scholar
  158. 158.
    Minowa T, Miwa S, Kobayashi S, Enoki T, Zhang XF, Komuro T, Iwamuro Y, Masaki T (1997) Inhibitory effect of nitrovasodilators and cyclic GMP on ET-1-activated Ca2+-permeable nonselective cation channel in rat aortic smooth muscle cells. Br J Pharmacol 120:1536–1544PubMedGoogle Scholar
  159. 159.
    Cornwell TL, Pryzwansky KB, Wyatt TA, Lincoln TM (1991) Regulation of sarcoplasmic reticulum protein phosphorylation by localized cyclic GMP-dependent protein kinase in vascular smooth muscle cells. Mol Pharmacol 40:923–931PubMedGoogle Scholar
  160. 160.
    Gibson A, McFadzean I, Tucker JF, Wayman C (1994) Variable potency of nitrergic-nitrovasodilator relaxations of the mouse anococcygeus against different forms of induced tone. Br J Pharmacol 113:1494–1500PubMedGoogle Scholar
  161. 161.
    Alewijnse AE, Peters SL, Michel MC (2004) Cardiovascular effects of sphingosine-1-phosphate and other sphingomyelin metabolites. Br J Pharmacol 143:666–684PubMedGoogle Scholar
  162. 162.
    Chatterjee S (1998) Sphingolipids in atherosclerosis and vascular biology. Arterioscler Thromb Vasc Biol 18:1523–1533PubMedGoogle Scholar
  163. 163.
    Cavalli AL, O’Brien NW, Barlow SB, Betto R, Glembotski CC, Palade PT, Sabbadini RA (2003) Expression and functional characterization of SCaMPER: a sphingolipid-modulated calcium channel of cardiomyocytes. Am J Physiol Cell Physiol 284:C780–C790PubMedGoogle Scholar
  164. 164.
    Condrescu M, Opuni K, Hantash BM, Reeves JP (2002) Cellular regulation of sodium–calcium exchange. Ann N Y Acad Sci 976:214–223PubMedCrossRefGoogle Scholar
  165. 165.
    Liu SJ, Kennedy RH (2003) Positive inotropic effect of ceramide in adult ventricular myocytes: mechanisms dissociated from its reduction in Ca2+ influx. Am J Physiol Heart Circ Physiol 285:H735–H744PubMedGoogle Scholar
  166. 166.
    Melendez AJ, Khaw AA (2002) Dichotomy of Ca2+ signals triggered by different phospholipid pathways in antigen stimulation of human mast cells. J Biol Chem 277:17255–17262PubMedGoogle Scholar
  167. 167.
    Schnurbus R, De Pietri Tonelli D, Grohovaz E, Zacchetti D (2002) Re-evaluation of primary structure, topology and localization of scamper, a putative intracellular Ca2+ channel activated by sphingosylphosphocholine. Biochem J 362:183–189PubMedGoogle Scholar
  168. 168.
    Ohya S, Tanaka M, Watanabe M, Maizumi Y (2000) Diverse expression of delayed rectifier K+ channel subtype transcription in several types of smooth muscle of the rat. J Smooth Muscle Res 36:101–115PubMedGoogle Scholar
  169. 169.
    Thorneloe KSD, Chen TT, Kerr PM, Grier EF, Horowitz B, Cole WC, Walsh MP (2001) Molecular composition of 4-aminopyridine-sensitive voltage gated K+ channels of vascular smooth muscle. Circ Res 89:1030–1037PubMedGoogle Scholar
  170. 170.
    Coussin F, Scott RH, Nixon GF (2003) Sphingosine 1-phosphate induces CREB activation in rat cerebral artery via a protein kinase C-mediated inhibition of voltage-gated K+ channels. Biochem Pharmacol 66:1861–1870PubMedGoogle Scholar
  171. 171.
    Levade T, Auge N, Veldman RJ, Cuvillier O, Negre- Salvayre A, Salvayre R (2001) Sphingolipid mediators in␣cardiovascular cell biology and pathology. Circ Res 89:957–968PubMedGoogle Scholar
  172. 172.
    Yatoni Y, Ruan F, Hakomori S, Igarashi Y (1995) Sphingosine-1-phosphate a platelet activating sphingolipid released from stimulated human platelets. Blood 86:193–202Google Scholar
  173. 173.
    Yatomi Y, Ohmori T, Rile G, Kazama F, Okamoto H, Sano T, Satoh K, Kume S, Tigyi G, Igarashi Y, Ozaki Y (2000) Sphingosine-1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells. Blood 96:343–348Google Scholar
  174. 174.
    Tokunou T, Ichiki T, Takeda K, Funakoshi Y, Lino N, Takeshita A (2001) cAMP response element-binding protein mediates thrombin-induced proliferation of vascular smooth muscle. Aterioscler Thromb Vasc Biol 21:176–179Google Scholar
  175. 175.
    Betto R, Teresi A, Turcato F, Salviati G, Sabbadini RA, Krown K, Glembotski CC, Kindman LA, Dettbarn C, Pereon Y, Yasui K, Palade PT (1997) Sphingosylphosphocholine modulates the ryanodine receptor/calcium-release channel of cardiac sarcoplasmic reticulum membranes. Biochem J 322:327–333PubMedGoogle Scholar
  176. 176.
    Jeon ES, Kang YJ, Song HY, Im DS, Kim HS, Ryu SH, Kim YK, Kim JH (2005) Sphingosylphosphorylcholine generates reactive oxygen species through calcium-, protein kinase Cδ- and phospholipase D-dependent pathways. Cell Signal 17:777–787PubMedGoogle Scholar
  177. 177.
    John S, Cesario D, Weiss JN (2003) Gap junctional hemichannels in the heart. Acta Physiol Scand 179:23–31PubMedGoogle Scholar
  178. 178.
    Henaff M, Antoine S, Mercadier JJ, Coulombe A, Hatem SN (2002) The voltage-independent B-type Ca2+ channel modulates apoptosis of cardiac myocytes. FASEB J 16:99–101PubMedGoogle Scholar
  179. 179.
    Pfeiffer C, Flemming B, Gunther J, Vetter R, Goos H, Pfeifer K (1978) Changes in the excitation contraction coupling in the myocardium of rabbits fed in a cholesterol-containing diet. Acta Biol Med Ger 37:1037–1047PubMedGoogle Scholar
  180. 180.
    Moffat MP, Dhalla NS (1985) Heart sarcolemmal ATPase and calcium binding activities in rats fed a high cholesterol diet. Can J Cardiol 1:194–200PubMedGoogle Scholar
  181. 181.
    Kutryk MJ, Pierce GN (1988) Stimulation of sodium–calcium exchange by cholesterol incorporation into isolated cardiac sarcolemmal vesicles. J Biol Chem 263:13167–13172PubMedGoogle Scholar
  182. 182.
    Dostanic I, Schultz JEJ, Lorenz JN, Lingrel JB (2004) The α-1 isoform of Na+/K+ ATPase regulates cardiac contractility and functionally interacts and colocalizes with the Na+/Ca2+ exchanger in heart. J Biol Chem 279:54053–54061PubMedGoogle Scholar
  183. 183.
    Orlowski J, Lingrel JB (1988) Tissue-specific and developmental regulation of rat Na+/K+ ATPase catalytic α isoform and β subunit mRNAs. J Biol Chem 263:10436–10442PubMedGoogle Scholar
  184. 184.
    Dostanic I, Lorenz JN, Schultz Jel J, Grupp IL, Neumann JC, Wani MA, Lingrel JB (2003) The α2 isoform of Na+/K+ ATPase mediates ouabain-induced cardiac inotropy in mice. J Biol Chem 278:53026–53034PubMedGoogle Scholar
  185. 185.
    Shao Q, Ren B, Elimban V, Tappia PS, Takeda N, Dhalla NS (2005) Modification of sarcolemmal Na+/K+ ATPase and Na+/Ca2+ exchanger expression in heart failure by blockade of rennin-angiotensin system. Am J Physiol 288:H2637–H2646Google Scholar
  186. 186.
    Dhalla NS, Dixon IMC, Rupp H, Barwinsky J (1992) Experimental congestive heart failure due to myocardial infarction: sarcolemmal receptors and cation transporters. Basic Res Cardiol 86:13–23Google Scholar
  187. 187.
    Gomez AM, Schwaller B, Porzig H, Vassort G, Niggli E, Egger M (2002) Increased exchange current but normal Ca2+ transport via Na+–Ca2+ exchange during cardiac hypertrophy after myocardial infarction. Circ Res 91:323–330PubMedGoogle Scholar
  188. 188.
    Despa S, Islam MA, Weber C, Pogwizelt SM, Bers DM (2002) Intracellular Na+ concentration is elevated in heart failure but Na+/K+ pump function is unchanged. Circulation 105:2543–2548PubMedGoogle Scholar
  189. 189.
    Ren B, Shao Q, Ganguly PK, Tappia PS, Takeda N, Dhalla NS (2005) Influence of long-term treatment of imidapril on mortality, cardiac function and gene expression in congestive heart failure due to myocardial infarction. Can J Physiol Pharmacol 82:1118–1127Google Scholar
  190. 190.
    Studer R, Reinecke H, Bilger J, Eschehagen T, Bohm M, Hasenfuss G, Just H, Holtz J, Drexler H (1994) Gene expression of the cardiac Na+/Ca2+ exchanger in end-stage human heart failure. Circ Res 75:443–453PubMedGoogle Scholar
  191. 191.
    Reinecke H, Studer R, Vetter R, Holtz J, Drexler H (1996) Cardiac Na+/Ca2+ exchange activity in patients with end-stage heart failure. Cardiovasc Res 31:48–54PubMedGoogle Scholar
  192. 192.
    Muller-Ehmsen J, McDonough AA, Farley RA, Schwinger H (2002) Sodium pump isoform expression in heart failure: implication for treatment. Basic Res Cardiol 97:125–130Google Scholar
  193. 193.
    Semb SO, Lunde PK, Holt E, Tonnessen T, Christensen G, Sejersted OM (1998) Reduced myocardial Na+/K+ ATPase pump capacity in congestive heart failure following myocardial infarction in rats. J Mol Cell Cardiol 30:1311–1328PubMedGoogle Scholar
  194. 194.
    Dixon IMC, Hata T, Dhalla NS (1992) Sarcolemmal Na+/K+ ATPase activity in congestive heart failure due to the myocardial infarction. Am J Physiol 262:C664–C671PubMedGoogle Scholar
  195. 195.
    Berridge MJ (2006) Remodelling Ca2+ signalling systems and cardiac hypertrophy. Biochem Soc Trans 34:228–231PubMedGoogle Scholar
  196. 196.
    Dorn GW 2nd, Force T (2005) Protein kinase C cascades in the regulation of cardiac hypertrophy. J Clin Invest 115:527–537PubMedGoogle Scholar
  197. 197.
    Ruf S, Piper M, Schluter KD (2002) Specific role for the extracellular signal regulated kinase pathway in angiotensin II but not phenylephrine-induced cardiac hypertrophy in vitro. Pflugers Arch 443:483–490PubMedGoogle Scholar
  198. 198.
    Chen CH, Gray MO, Mochly-Rosen D (1999) Cardioprotection from ischemia by a brief exposure to physiological levels of ethanol: role of ε protein kinase C. Proc Natl Acad Sci (USA) 96:12784–12789Google Scholar
  199. 199.
    Wakasaki H, Koya D, Schoen FJ, Jirousek MR, Ways DK, Hoit BD, Walsh RA, King GL (1997) Targeted overexpression of protein kinase Cβ2 isoform in myocardium causes cardiomyopathy. Proc Natl Acad Sci (USA) 94:9320–9325Google Scholar
  200. 200.
    Takeishi Y, Chu G, Kirkpatrick DM, Li Z, Wakasaki H, Kranias EG, King GL, Walsh RA (1998) In vivo phosphorylation of cardiac troponin I by protein kinase Cβ2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts. J Clin Invest 102:72–78PubMedGoogle Scholar
  201. 201.
    Mochly-Rosen D, Wu G, Hahn H, Osinska H, Liron T, Lorenz JN, Yatani A, Robbins J, Dorn GW 2nd (2000) Cardiotrophic effects of protein kinase Cε: analysis by in vivo modulation of PKCε translocation. Circ Res 86:1173–1179Google Scholar
  202. 202.
    Kang SM, Lim S, Song H, Chang W, Lee S, Bae SM, Chung JH, Lee H, Kim HG, Yoon DH, Kim TW, Jang Y, Sung JM, Chung NS, Hwang KC (2006) Allopurinol modulates reactive oxygen species generation and Ca2+ overload in ischemia reperfused heart and hypoxia-reoxygenated cardiomyocytes. Eur J Pharmacol 535:212–219PubMedGoogle Scholar
  203. 203.
    Palomeque J, Sapia L, Hajjar RJ, Mattiazzi A, Vila Petroff M (2006) Angiotensin II-induced negative inotropy in rat ventricular myocytes: role of reactive oxygen species and p38MAPK. Am J Physiol Heart Circ Physiol 290:H96–H106PubMedGoogle Scholar
  204. 204.
    Lim HW, New L, Han J, Molkentin JD (2001) Calcineurin enhances MAPK phosphatase-1 expression and p38MAPK inactivation in cardiac myocytess. J Biol Chem 276:15913–15919PubMedGoogle Scholar
  205. 205.
    Garrington TP, Johnson GL (1999) Organization and regulation of mitogen activated protein kinase signaling pathways. Curr Opin Cell Biol 11:211–218PubMedGoogle Scholar
  206. 206.
    Bogoyevitch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH (1996) Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circ Res 79:162–173PubMedGoogle Scholar
  207. 207.
    Gillespie-Brown J, Fuller SJ, Bogoyevitch MA, Cowley S, Sugden PH (1995) The mitogen activated protein kinase kinase. MMEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes. J Biol Chem 270:28092–28096Google Scholar
  208. 208.
    Glennon PE, Kaddoura S, Sale EM, Sale GJ, Fuller SJ, Sugden PH (1996) Depletion of mitogen activated protein kinase using an antisense oligodeoxynucleotide approach down regulates the phenylephrine induced hypertrophic response in rat cardiac myocytes. Circ Res 78:954–961PubMedGoogle Scholar
  209. 209.
    Clerk A, Michael A, Sugden PHH (1998) Stimulation of the p38 mitogen activated protein kinase kinase pathway in neonatal rat ventricular myocytes by the G protein coupled receptor agonists endothelin-1 and phenylephrine. A role in cardiac myocyte hypertrophy? J Cell Biol 142:523–535PubMedGoogle Scholar
  210. 210.
    Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto KI (1999) JSAPI, a novel Jun N-terminal protein kinase kinase (JNK) binding protein that functions as a scaffold factor in the JNK signaling. Mol Cell Biol 19:7539–7548PubMedGoogle Scholar
  211. 211.
    Cook SA, Sugden PH, Clerk A (1999) Actvation of c-Jun N-terminal kinases and p38 mitogen activated protein kinases in human heart failure secondary to ischemic heart disease. J Mol Cell Cardiol 31:1429–1434PubMedGoogle Scholar
  212. 212.
    Ramirez MT, Sah VP, Zhao XL, Hunter JJ, Chien KR, Brown JH (1997) The MEKK-JNK pathway is stimulated by α-1-adrenergic receptor and ras activation and is associated with in vitro and in vivo cardiac hypertrophy. J Biol Chem 272:14057–14061PubMedGoogle Scholar
  213. 213.
    Nemoto S, Sheng Z, Lin A (1998) Opposing effects of Jun kinase and p38 mitogen activated protein kinases on cardiomyocyte hypertrophy. Mol Cell Biol 18:3518–3526PubMedGoogle Scholar
  214. 214.
    Choukroun G, Hajjar R, Fry S, del Monte F, Haq S (1999) Regulation of cardiac hypertrophy in vivo by the stress activated protein kinases/c-Jun NH2 terminal kinases. J Clin Invest 104:391–398PubMedCrossRefGoogle Scholar
  215. 215.
    Anis Y (2006) Involvement of Ca2+ in the apoptotic process – friends or foes. Pathways. Issue no 2, (Alomone labs, Jerusalem, Israel) Spring, pp 2–7Google Scholar
  216. 216.
    Tzanidis A, Lim S, Hannan RD, See F, Ugoni AM, Krum H (2001) Combined angiotensin and endothelin receptor blockade attenuates adverse cardiac remodeling post-myocardial infarction in the rat: possible role of transforming growth factor β(1). J Mol Cell Cardiol 33:969–981PubMedGoogle Scholar
  217. 217.
    Ruwhof C, van der Laarse A (2000) Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res 47:23–37PubMedGoogle Scholar
  218. 218.
    Heidkamp MC, Scully BT, Vijayan K, Engman SJ, Szotek EL, Samarel AM (2005) PYK2 regulate SERCA2 gene expression in neonatal rat ventricular myocytes. Am J Physiol 289:C471–C482Google Scholar
  219. 219.
    Rothstein EC, Byron KL, Reed RE, Fliegel L, Lucchesi PA (2002) H2O2-induced Ca2+ overload in NRVM involves ERK1/2 MAP kinases: role for an NHE-1-dependent pathway. Am J Physiol Heart Circ Physiol 283:H598–H605PubMedGoogle Scholar
  220. 220.
    Menick DR, Xu L, Kappler C, Jiang W, Withers P, Shepherd N, Conway SJ, Muller JG (2002) Pathways regulating Na+/Ca2+ exchanger expression in the heart. Ann NY Acad Sci 976:237–247PubMedCrossRefGoogle Scholar
  221. 221.
    Tian J, Gong X, Xie Z (2001) Signal-transducing function of Na+/K+-ATPase is essential for ouabain’s effect on (Ca2+)i in rat cardiac myocytes. Am J Physiol Heart Circ Physiol 281:H1899–H1907PubMedGoogle Scholar
  222. 222.
    Kometiani P, Li J, Gnudi L, Kahn BB, Askari A, Xie Z (1998) Multiple signal transduction pathways link Na+/K+-ATPase to growth-related genes in cardiac myocytes. The roles of Ras and mitogen-activated protein kinases. J Biol Chem 273:15249–15256PubMedGoogle Scholar
  223. 223.
    Tokudome T, Horio T, Soeki T, Mori K, Kishimoto I, Suga S, Yoshihara F, Kawano Y, Kohno M, Kangawa K (2004) Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy: interference between CNP and endothelin-1 signaling pathways. Endocrinology 145:2131–2140PubMedGoogle Scholar
  224. 224.
    Katoh N, Wise BC, Kuo JF (1983) Phosphorylation of cardiac troponin inhibitory subunit (troponin I) and tropomyosin binding subunit (troponin T) by cardiac phospholipid sensitive calcium dependent protein kinase. Biochem J 209:189–195PubMedGoogle Scholar
  225. 225.
    Liao P, Wang SQ, Wang S, Zheng M, Zheng M, Zhang SJ, Cheng H, Wang Y, Xiao RP (2002) p38 Mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes. Circ Res 90:190–196PubMedGoogle Scholar
  226. 226.
    Chen Y, Rajashree R, Liu Q, Hofmann P (2003) Acute p38MAPK activation decreases force development in ventricular myocytes. Am J Physiol 285:H2578–H2586Google Scholar
  227. 227.
    Communal C, Sumandea M, de Tombe P, Norula J, Solaro RJ, Hajjar RJ (2002) Functional consequences of caspase activation in cardiac myocytes. Proc Natl Acad Sci (USA) 99:6252–6256Google Scholar
  228. 228.
    Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG (2001) Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. Am J Physiol Heart Circ Physiol 281:H2337–H2365PubMedGoogle Scholar
  229. 229.
    Hiroi Y, Hiroi J, Kudoh S, Yazaki Y, Nagai (2001) Two distinct mechanisms of angiotensin II-induced negative regulation of the mitogen-activated protein kinases in cultured cardiac myocytes. Hypertens Res 24:385–394Google Scholar
  230. 230.
    Tfelt-Hansen J, Hansen JL, Smajilovic S, Terwillinger EF, Haunso S, Sheikh SP (2006) Calcium receptor is functionally expressed in rat neonatal ventricular myocytes. Am J Physiol 290:H1165–H1171Google Scholar
  231. 231.
    Lin KI, Chattopadhyay N, Bai M, Alvarez R, Dang CV, Baraban JM, Brown EM, Ratan RR (1998) Elevated extracellular calcium can prevent apoptosis via the calcium-sensing receptor. Biochem Biophys Res Commun 249:325–331PubMedGoogle Scholar
  232. 232.
    Tfelt-Hansen J, Chattopadhyay N, Yano S, Kanuparthi D, Rooney P, Schwarz P, Brown EM (2004) Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. Endocrinology 145:1211–1217PubMedGoogle Scholar
  233. 233.
    Communal C, Singh K, Sawyer DB, Colucci WS (1999) Opposing effects of β1 and β2 adrenergic receptors on cardiac myocyte apoptosis: role of a pertussis toxin sensitive G protein. Circulation 100:2210–2212PubMedGoogle Scholar
  234. 234.
    Bennet MR (2002) Apoptosis in the cardiovascular system. Heart 87:480–487Google Scholar
  235. 235.
    Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AN, Rector T (1984) Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 3411:819–823CrossRefGoogle Scholar
  236. 236.
    Qin F, Rounds NK, Mao W, Kawai K, Liang CS (2001) Antioxidant vitamins prevent cardiomyocyte apoptosis produced by norepinephrine infusion in ferrets. Cardiovasc Res 51:736–748PubMedGoogle Scholar
  237. 237.
    Patil C, Walter P (2001) Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr Opin Cell Biol 13:349–356PubMedGoogle Scholar
  238. 238.
    Jones SE, Jomary C (2002) Clusterin. Int J Biochem Cell Biol 34:427–431PubMedGoogle Scholar
  239. 239.
    Rao RV, Peel A, Logvinova A, del Rio G, Hermal E, Yokota T, Goldsmith PC, Ellerby LM, Ellerby HM, Bredesen DE (2002) Coupling endoplasmic reticular stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett 514:122–128PubMedGoogle Scholar
  240. 240.
    Dostanic S, Servant N, Wang C, Chalifour LE (2004) Chronic β adrenoceptor stimulation in vivo decreased Bcl-2 and increased Bax expression but did not activate apoptotic pathways in mouse heart. Can J Physiol Pharmacol 82:167–174PubMedGoogle Scholar
  241. 241.
    Distelhorst CW, Lam M, McCormick TS (1996) Bcl-2 inhibits hydrogen peroxide induced ER Ca2+ pool depletion. Oncogene 12:2051–2055PubMedGoogle Scholar
  242. 242.
    Kuo TH, Choi Kim H-R, Zhu L, Yu Y, Lin H-M, Tsang W (1998) Modulation of endoplasmic reticulum calcium pump by Bcl-2. Oncogene 17:1903–1910PubMedGoogle Scholar
  243. 243.
    Wuytack F, Raeymaekers L, Missiaen L (2002) Molecular physiology of the SERCA and SPCA pumps. Cell Calcium 32:279–305PubMedGoogle Scholar
  244. 244.
    Kusuoka H, Marban E (1992) Cellular mechanisms of myocardial stunning. Ann Rev Physiol 54:243–256Google Scholar
  245. 245.
    Sylvester JT (2001) Hypoxic pulmonary vasoconstriction: a radical view. Circ Res 88:1228–1230PubMedGoogle Scholar
  246. 246.
    Post JM, Gelband CH, Hume JR (1995) (Ca2+)i inhibition of K+ channels in canine pulmonary artery. Novel mechanism for hypoxia-induced membrane depolarization. Circ Res 77:131–139PubMedGoogle Scholar
  247. 247.
    Hirota K, Fukuda R, Takabuchi S, Kizaka-Kondoh S, Adachi T, Fukuda K, Semenza GL (2004) Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signaling. J Biol Chem 279:41521–41528PubMedGoogle Scholar
  248. 248.
    Date T, Mochizuki S, Belanger AJ, Yamakawa M, Luo Z, Vincent KA, Cheng SH, Gregory RJ, Jiang C (2005) Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury. Am J Physiol Cell Physiol 288:C314–C320PubMedGoogle Scholar
  249. 249.
    Voelkel NF, Cool C, Taraceviene-Stewart L, Geraci MW, Yeager M, Bull T, Kasper M, Tuder RM (2002) Janus face of vascular endothelial growth factor: the obligatory survival factor for lung vascular endothelium controls precapillary artery remodeling in severe pulmonary hypertension. Crit Care Med 30(5 Suppl):S251–S256PubMedGoogle Scholar
  250. 250.
    Kim CH, Cho YS, Chun YS, Park JW, Kim MS (2002) Early expression of myocardial HIF-1α in response to mechanical stresses: regulation by stretch-activated channels and the phosphatidylinositol 3-kinase signaling pathway. Circ Res 90:E25–E33PubMedGoogle Scholar
  251. 251.
    Krause SM, Jacobus WE, Becker LC (1989) Alterations in cardiac sarcoplasmic reticulum calcium transport n the post ischemic “stunned myocardium”. Circ Res 65:526–530PubMedGoogle Scholar
  252. 252.
    Kukreja RC, Kontos MC, Loesser KE, Batra SK, Qian YZ, Gbur CJ Jr, Naseem SA, Jesse RL, Hess ML (1994) Oxidant stress increases heat shock protein 70 mRNA in isolated perfused rat heart. Am J Physiol 267:H2213–H2219PubMedGoogle Scholar
  253. 253.
    Rothman JE (1989) Polypeptide chain binding proteins: cataysis of protein folding and related processes in cells. Cell 59:591–601PubMedGoogle Scholar
  254. 254.
    Hess ML, Kukreja RC (1995) Free radicals, calcium homeostasis, heat shock proteins and myocardial stunning. Ann Thorac Surg 60:760–766PubMedGoogle Scholar
  255. 255.
    Currie RW (1987) Effects of ischemia and perfusion temperature on the synthesis of stress induced (heat shock) proteins in isolated and perfused rat hears. J Mol Cell Cardiol 19:795–808PubMedGoogle Scholar
  256. 256.
    Landry SM, Gierasch LM (1991) Recognition of nascent polypeptides for targeting and folding. Trends Biochem Sci 16:159–163PubMedGoogle Scholar
  257. 257.
    Murakami H, Pain D, Blobel G (1987) 70 kDa heat shock-related protein is one of at least two distinct cytosolic factors stimulating protein import into mitochondria. J Cell Biol 107:2051–2057Google Scholar
  258. 258.
    Marber MS, Mestril R, Yelon DM, Dillmann WH (1994) A␣heat shock protein 70 transgene results in myocardial protection (Abstract). Circulation 90(Suppl 1):2883Google Scholar
  259. 259.
    Qian Y-Z, Kontos MC, Gu Y, Kukreja RC (1994) Quercetin blocks ischemic tolerance in heat stressed rat hearts (Abstract). Circulation 90(Suppl 1):2883Google Scholar
  260. 260.
    Kukreja RC, Qian Y-Z, Kontos MC, Hess ML (1995) Quercetin blocks ischemic tolerance and synthesis of HSP 70 in rat hearts (Abstract). J Cell Biochem 19B:219Google Scholar
  261. 261.
    Sakai S, Miyauchi T, Sakurai T, Kasuya T, Ihara M, Yamaguchi I, Goto K, Sugishita Y (1996) Endogenous endothelin-1 participates in the maintenance of cardiac function in rat with congestive heart failure: marked increase in endothelin-1production in the failing heart. Circulation 93:1214–1222PubMedGoogle Scholar
  262. 262.
    Chu L, Takahashi R, Norota I, Miyamoto T, Takeishi Y, Ishii K, Kuboto II, Endoh M (2003) Signal transduction and calcium signaling in contractile regulation induced by cross-talk between endothelin-1 and norepinephrine in dog ventricular myocardium. Circ Res 92:1024–1032PubMedGoogle Scholar
  263. 263.
    Takanashi M, Endoh M (1991) Characterization of positive inotropic effect of endothelin on mammalian ventricular myocardium. Am J Physiol 261:H611–H619PubMedGoogle Scholar
  264. 264.
    Watanabe T, Endoh M (1999) Characterization of the endothelin-1 induced regulation of L-type Ca2+ current in rabbit ventricular myocytes. Naumyn Schniedebergs Arch Pharmacol 360:654–664Google Scholar
  265. 265.
    Yang HT, Sakurai K, Sugawara H, Watanabe T, Norota I, Endoh M (1999) Role of Na+/Ca2+ exchange in endothelin-1 induced increases in Ca2+ transient and contractility in rabbit ventricular myocytes: pharmacological analysis with KB-R7943. Br J Pharmacol 126:1785–1795PubMedGoogle Scholar
  266. 266.
    Watanabe T, Endoh M (2000) Antiadrenergic effects of endothelin-1 on L-type Ca2+ current in cannine ventricular myocytes. J Cardiovasc Pharmacol 36:344–350PubMedGoogle Scholar
  267. 267.
    Sharikabad MN, Ostbye KM, Brors O (2001) Increased [Mg2+]o reduces Ca2+ influx and disruption of mitochondrial membrane potential during reoxygenation. Am J Physiol 281:H2113–H2123Google Scholar
  268. 268.
    Brunet S, Scheuer T, Klevit R, Catterall WA (2005) Modulation of Cav1.2 channels by Mg2+ acting at an E-F hand motif in the COOH terminal domain. J Gen Physiol 126:311–323PubMedGoogle Scholar
  269. 269.
    Kh R, Khullar M, Kashyap M, Pandhi P, Uppal R (2000) Effect of oral magnesium supplementation on blood pressure, platelet aggregation and calcium handling in deoxycortisone acetate induced hypertension in rats. J Hypertens 18:919–926PubMedGoogle Scholar
  270. 270.
    Berthelot A, Luthringer C, Meyers E, Exinger A (1997) Disturbance of magnesium metabolism in the spontaneously hypertensive rat. J Am Coll Nutr 6:329–332Google Scholar
  271. 271.
    Kosso KL, Grubbs RD (1994) Elevated extracellular Mg2+ increases Mg2+ buffering through a Ca2+ dependent mechanism in cardiomyocytes. Am J Physiol 267:C633–C641Google Scholar
  272. 272.
    Schwinger RHJ, Bohm M, Uhlman R, Schmid U, Uberfuler R, Krenger E, Reichat B, Erdman E (1993) Magnesium restores the altered force-frequency relationship in failing human myocardium. Am Heart J 126:1018–1021PubMedGoogle Scholar
  273. 273.
    Kin SJ, Kang HS, Kang MS, Yu X, Park SY, Kim IS, Kim NS, Kim SZ, Kwak YG, Kim JS (2005) α(1)-agonists-induced Mg2+ efflux is related to MAP kinase activation in the heart. Biochem Biophys Res Commun 333:1132–1138Google Scholar
  274. 274.
    Kawano S (1998) Dual mechanisms of Mg2+ block of ryanodine receptor Ca2+ release channel from cardiac sarcoplasmic reticulum. Recept Channels 5:405–416PubMedGoogle Scholar
  275. 275.
    Saris NE, Mervaala E, Karppanern H, Khawaja JL, Lewenstam A (2000) Magnesium: an update on physiological, clinical and analytical aspects. Clin Chim Acta 294:1–26PubMedGoogle Scholar
  276. 276.
    Gunther T (1993) Mechanisms and regulation of Mg2+ efflux and Mg2+ influx. Miner Electrolyte Metab 19:259–265PubMedGoogle Scholar
  277. 277.
    Yamaoka K, Seyama I (1998) Phosphorylation modulates L-type Ca2+ channels in frog ventricular myocytes by changes in sensitivity to Mg2+ block. Pflügers Arch – Eur J Physiol 435:329–337Google Scholar
  278. 278.
    Chakraborti S, Chakraborti T, Mandal M, Mandal A, Das S, Ghosh S (2002) Protective role of magnesium in cardiovascular diseases: a review. Mol Cell Biochem 238:163–179PubMedGoogle Scholar
  279. 279.
    Morita H, Seidman J, Seidman CE (2005) Genetic causes of human heart failure. J Clin Invest 115:518–526PubMedGoogle Scholar
  280. 280.
    Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V, Danieli GA (2001) Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103:196–200PubMedGoogle Scholar
  281. 281.
    Marks AR, Priori S, Memmi M, Kontula K, Laitinen PJ (2002) Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polynorphic ventricular tachycardia. J Cell Physiol 190:1–6PubMedGoogle Scholar
  282. 282.
    Wehrens XH, Lehnart SE, Huang F, Vest JA, Reiken SR, Mohler PJ, Sun J, Guatimosim S, Song LS, Rosemblit N, D’Armiento JM, Napolitano C, Memmi M, Priori SG, Lederer WJ, Marks AR (2003) KBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 113:829–840PubMedGoogle Scholar
  283. 283.
    Jiang D, Xiao B, Yang D, Wang R, Choi P, Zhang L, Cheng H, Chen SR (2004) RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR). Proc Natl Acad Sci (USA) 101:13062–13067Google Scholar
  284. 284.
    Clozel JP, Ertel EA, Ertel SI (1999) Voltage-gated T-type Ca2+ channels and heart failure. Proc Assoc Am Physicians 111:429–437PubMedGoogle Scholar
  285. 285.
    Wu SN, Wu AZ, Lin MW (2006) Pharmacological roles of the large-conductance calcium-activated potassium channel. Curr Top Med Chem 6:1025–1030PubMedGoogle Scholar
  286. 286.
    Picano E (2001) Dipyridamole in chronic stable angina pectoris. A randomized, double blind, placebo-controlled, parallel group study. On behalf of the persatin in stable angina (PISA) study group. Eur Heart J 22:1785–1793PubMedGoogle Scholar
  287. 287.
    Chaitman BR (2004) Efficacy and safety of a metabolic modulator drug in chronic stable angina: review of evidence from clinical trials. J Cardiovasc Pharmacol Ther 9(Suppl 1):S47–S64PubMedGoogle Scholar
  288. 288.
    Okuda S, Yano M, Doi M, Oda T, Tokuhisa T, Kohno M, Kobayashi S, Yamamoto T, Ohkusa T, Matsuzaki M (2004) Valsartan restores sarcoplasmic reticulum function with no appreciable effect on resting cardiac function in pacing-induced heart failure. Circulation 109:911–919PubMedGoogle Scholar
  289. 289.
    Kimura J, Kawahara M, Sakai E, Yatabe J, Nakanishi H (1999) Effects of a novel cardioprotective drug, JTV-519, membrane currents of guinea pig ventricular myocytes. Jpn J Pharmacol 79:275–281PubMedGoogle Scholar
  290. 290.
    Nagle DG, Zhou YD (2006) Natural product-derived small molecule activators of hypoxia-inducible factor-1 (HIF-1). Curr Pharm Des 12:2673–2688PubMedGoogle Scholar
  291. 291.
    Sierevogel MJ, Pasterkamp G, de Kleijn DP, Strauss BH (2003) Matrix metalloproteinases: a therapeutic target in cardiovascular disease. Curr Pharm Des 9:1033–1040PubMedGoogle Scholar
  292. 292.
    Wehrens XH, Lehnart SE, Marks AR (2005) Intracellular calcium release and cardiac disease. Annu Rev Physiol 67:69–98PubMedGoogle Scholar
  293. 293.
    Sipido KR, Carmeliet E, Van de Werf F (1998) T-type Ca2+ current as a trigger for Ca2+ release from the sarcoplasmic reticulum in guinea-pig ventricular myocytes. J Physiol 508:439–451PubMedGoogle Scholar
  294. 294.
    Lytton J, Westlin M, Hanley MR (1991) Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca2+-ATPase family of calcium pumps. J Biol Chem 266:17067–17071PubMedGoogle Scholar
  295. 295.
    Koss KL, Grupp IL, Kranias EG (1997) The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility. Basic Res Cardiol 92(Suppl 1):17–24Google Scholar
  296. 296.
    Jones LR, Simmerman HK, Wilson WW, Gurd FR, Wegner AD (1895) Purification and characterization of phospholamban from canine cardiac sarcoplasmic reticulum. J Biol Chem 260:7721–7730Google Scholar
  297. 297.
    Bers DM, Bridge JH (1989) Relaxation of rabbit ventricular muscle by Na+/Ca2+ exchange and sarcoplasmic reticulum calcium pump. Ryanodine and voltage sensitivity. Circ Res 65:334–342PubMedGoogle Scholar
  298. 298.
    Gomez AM, Valdivia HH, Cheng H, Lederer MR, Santana LF, Cannell MB, McCune SA, Altschuld RA, Lederer WJ (1997) Defective excitation–contraction coupling in experimental cardiac hypertrophy and heart failure. Science 276:800–806PubMedGoogle Scholar
  299. 299.
    Bueckelmann DJ, Nabauer M, Erdmann E (1992) Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 85:1046–1055Google Scholar
  300. 300.
    Hasenfuss G, Mulieri LA, Leavitt BJ, Allen PD, Haeberle JR, Alpert NR (1992) Alteration of contractile function and excitation–contraction coupling in dilated cardiomyopathy. Circ Res 70:1225–1232PubMedGoogle Scholar
  301. 301.
    Putney JW Jr, Ribeiro CMP (2000) Signaling pathways between the plasma membrane and endoplasmic reticulum calcium stores. Cell Mol Life Sci 57:1272–1286PubMedGoogle Scholar
  302. 302.
    Irvine RF (1990) ‘Quantal’ Ca2+ release and the control of Ca2+ entry by inositol phosphates–a possible mechanism. FEBS Lett 263:5–9PubMedGoogle Scholar
  303. 303.
    Zhu WZ, Wang SQ, Chakir K, Yang D, Zhang T, Brown JH, Devic E, Kobilka BK, Cheng H, Xiao RP (2003) Linkage of β1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II. J Clin Invest 111:617–625PubMedGoogle Scholar
  304. 304.
    Marks AR (2003) Calcium and the heart: a question of life and death. J Clin Invest 111:597–600PubMedGoogle Scholar
  305. 305.
    Cigolani HE, Ennis IL, Mosca SM (2003) NHE-1 and NHE-6 activities. Ischemic and reperfusion injury. Circ Res 93:694–696Google Scholar
  306. 306.
    Guerini D (1998) The significance of the isoforms of plasma membrane Ca2+-ATPase. Cell Tissue Res 292:191–197PubMedGoogle Scholar
  307. 307.
    Aviv A (1996) Recent advances in cellular calcium homeostasis: implications to altered regulation of cellular calcium and Na+/H+ exchange in essential hypertension. Curr Opinn Card 11:427–482Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Sajal Chakraborti
    • 1
  • Sudip Das
    • 1
  • Pulak Kar
    • 1
  • Biswarup Ghosh
    • 1
  • Krishna Samanta
    • 1
  • Saurav Kolley
    • 2
  • Samarendranath Ghosh
    • 3
  • Soumitra Roy
    • 1
  • Tapati Chakraborti
    • 1
  1. 1.Department of Biochemistry and BiophysicsUniversity of KalyaniKalyaniIndia
  2. 2.Department of CardiologyBelle Vue ClinicKolkataIndia
  3. 3.Bangur Institute of NeurologyKolkataIndia

Personalised recommendations