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Rapid Signaling Pathways

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Signaling in the Heart

Abstract

Recent evidence has shown that in the heart a plurality of receptor systems regulate heart rate and the force of contraction. A number of cardiac receptors are targets for neurotransmitters released from sympathetic and parasympathetic neurons innervating the myocardium. Other cardiac receptors transduce signals from circulating hormones as well as from several paracrine factors. In this chapter, we describe the structural and functional aspects of major signaling pathways participating in the contractile activity of normal healthy myocardium.

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References

  1. Elliott TR. On the action of adrenalin. J Physiol (London). 1904;31:20–1.

    Google Scholar 

  2. von Euler US. A specific sympathomimetic ergone in adrenergic nerve fibres (sympathin) and its relation to adrenaline and noradrenaline. Acta Physiol Scand. 1946;12:73–97.

    Article  Google Scholar 

  3. Vago T, Bevilacqua M, Dagani R, Meroni R, Frigeni G, Santoliss C, et al. Comparison of rat and human left ventricle beta-adrenergic receptors: subtype heterogeneity delineated by direct radioligand binding. Biochem Biophys Res Commun. 1984;121:346–54.

    Article  PubMed  CAS  Google Scholar 

  4. Hedberg A, Minneman KP, Molinoff PB. Differential distribution of beta-1 and beta-2 adrenergic receptors in cat and guinea-pig heart. J Pharmacol Exp Ther. 1980;212:503–8.

    PubMed  CAS  Google Scholar 

  5. Gauthier C, Tavernier G, Charpentier F, Langin D, Le Marec H. Functional beta 3-adrenoceptor in the human heart. J Clin Invest. 1996;98:556–62.

    Article  PubMed  CAS  Google Scholar 

  6. Ping P, Hammond HK. Diverse G protein and beta-adrenergic receptor mRNA expression in normal and failing porcine hearts. Am J Physiol. 1994;267:H2079–85.

    PubMed  CAS  Google Scholar 

  7. Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, et al. Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res. 1986;59:297–309.

    PubMed  CAS  Google Scholar 

  8. Motomura S, Reinhard-Zerkowski H, Daul A, Brodde OE. On the physiologic role of beta-2 adrenoceptors in the human heart: in vitro and in vivo studies. Am Heart J. 1990;119:608–19.

    Article  PubMed  CAS  Google Scholar 

  9. Bean BP. Two kinds of calcium channels in canine atrial cells: differences in kinetics, selectivity, and pharmacology. J Gen Physiol. 1985;86:1–30.

    Article  PubMed  CAS  Google Scholar 

  10. Hagiwara N, Irisawa H, Kameyama M. Contribution of two types of calcium currents to the pacemaker potentials of rabbit sine-atrial node cells. J Physiol. 1988;395:233–53.

    PubMed  CAS  Google Scholar 

  11. Hartzell HC. Regulation of cardiac ion channels by catecholamines, acetylcholine and second messenger systems. Prog Biophys Mol Biol. 1988;52:165–247.

    Article  PubMed  CAS  Google Scholar 

  12. Shimoni Y. Hormonal control of cardiac ion channels and transporters. Prog Biophys Mol Biol. 1999;72:67–108.

    Article  PubMed  CAS  Google Scholar 

  13. De Jongh KS, Murphy BJ, Colvin AA, Hell JW, Takahashi M, Catterall WA. Specific phosphorylation of a site in the full-length form of the alpha 1 subunit of the cardiac L-type calcium channel by adenosine 3′,5′-cyclic monophosphate dependent protein kinase. Biochemistry. 1996;35:10392–402.

    Article  PubMed  Google Scholar 

  14. McDonald TF, Pelzer S, Trautwein W, Pelzer DJ. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol Rev. 1994;74:365–507.

    PubMed  CAS  Google Scholar 

  15. Gerhardstein BL, Puri TS, Chien AJ, Hosey MM. Identification of the sites phosphorylated by cyclic AMP-dependent protein kinase on the β2 subunit of L-type voltage-dependent calcium channels. Biochemistry. 1999;38:10361–70.

    Article  PubMed  CAS  Google Scholar 

  16. Yatani A, Codina J, Imoto Y, Reeves JP, Birnbaumer L, Brown AM. A G protein directly regulates mammalian cardiac calcium channels. Science. 1987;238:1288–92.

    Article  PubMed  CAS  Google Scholar 

  17. Luo W, Chu G, Sato Y, Zhou Z, Kadambi VJ, Kranias EG. Transgenic approaches to define the functional role of dual site phospholamban phosphorylation. J Biol Chem. 1998;273:4734–9.

    Article  PubMed  CAS  Google Scholar 

  18. Takimoto E, Soergel DG, Janssen PM, Stull LB, Kass DA, Murphy AM. Frequency- and afterload-dependent cardiac modulation in vivo by troponin I with constitutively active protein kinase A phosphorylation sites. Circ Res. 2004;94:496–504.

    Article  PubMed  CAS  Google Scholar 

  19. Yasuda S, Coutu P, Sadayappan S, Robbins J, Metzger JM. Cardiac transgenic and gene transfer strategies converge to support an important role for troponin I in regulating relaxation in cardiac myocytes. Circ Res. 2007;101:377–86.

    Article  PubMed  CAS  Google Scholar 

  20. Solaro RJ, Rosevear P, Kobayashi T. The unique functions of cardiac troponin I in the control of cardiac muscle contraction and relaxation. Biochem Biophys Res Commun. 2008;369:82–7.

    Article  PubMed  CAS  Google Scholar 

  21. Christ T, Galindo-Tovar A, Thoms M, Ravens U, Kaumann AJ. Inotropy and L-type Ca2+ current, activated by β1- and β2-adrenoceptors, are differently controlled by phosphodiesterases 3 and 4 in rat heart. Br J Pharmacol. 2009;156:62–83.

    Article  PubMed  CAS  Google Scholar 

  22. Pitcher JA, Touhara K, Payne ES, Lefkowitz RJ. Pleckstrin homology domain-mediated membrane association and activation of the beta-adrenergic receptor kinase requires coordinate interaction with G beta gamma subunits and lipid. J Biol Chem. 1995;270:11707–10.

    Article  PubMed  CAS  Google Scholar 

  23. Nantel F, Bonin H, Emorine LJ, Zilberfarb V, Strosberg AD, Bouvier M, et al. The human beta 3-adrenergic receptor is resistant to short term agonist-promoted desensitization. Mol Pharmacol. 1993;43:548–55.

    PubMed  CAS  Google Scholar 

  24. Goodman Jr OB, Krupnick JG, Santini F, Gurevich VV, Penn RB, Gagnon AW, et al. Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor. Nature. 1996;383:447–50.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang J, Barak LS, Winkler KE, Caron MG, Ferguson SS. A central role for beta-arrestins and clathrin-coated vesicle-mediated endocytosis in beta2-adrenergic receptor resensitization. Differential regulation of receptor resensitization in two distinct cell types. J Biol Chem. 1997;272:27005–14.

    Article  PubMed  CAS  Google Scholar 

  26. Gauthier C, Langin D, Balligand JL. β3-Adrenoceptors in the cardiovascular system. Trends Pharmacol Sci. 2000;21:426–31.

    Article  PubMed  CAS  Google Scholar 

  27. Endoh M. Cardiac alpha(1)-adrenoceptors that regulate contractile function: subtypes and subcellular signal transduction mechanisms. Neurochem Res. 1996;21:217–29.

    Article  PubMed  CAS  Google Scholar 

  28. Ruffolo RR, Hollinger MA, editors. G-Protein coupled transmembrane signaling mechanisms. Boca Raton: CRC Press; 1995. p. 1–34.

    Google Scholar 

  29. Perrella MA, Maki T, Prasad S, Pimental D, Singh K, Takahashi N, et al. Regulation of heparin-binding epidermal growth factor-like growth factor mRNA levels by hypertrophic stimuli in neonatal and adult rat cardiac myocytes. J Biol Chem. 1994;269:27045–50.

    PubMed  CAS  Google Scholar 

  30. Rump LC, Riera-Knorrenschild G, Schwertfeger E, Bohmann C, Spillner G, Schollmeyer P. Dopaminergic and α-adrenergic control of neurotransmission in human right atrium. J Cardiovasc Pharmacol. 1995;26:462–70.

    Article  PubMed  CAS  Google Scholar 

  31. Wang Z, Shi H, Wang H. Functional M3 muscarinic acetylcholine receptors in mammalian hearts. Br J Pharmacol. 2004;142:395–408.

    Article  PubMed  CAS  Google Scholar 

  32. Brodde OE, Broede A, Daul A, Kunde K, Michel MC. Receptor systems in the non-failing human heart. Basic Res Cardiol. 1992;87 Suppl 1:1–14.

    PubMed  CAS  Google Scholar 

  33. Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983;301:569–74.

    Article  PubMed  CAS  Google Scholar 

  34. Han X, Kubota I, Feron O, Opel DJ, Arstall MA, Zhao Y-Y, et al. Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase (eNOS). Proc Natl Acad Sci USA. 1998;95:6510–5.

    Article  PubMed  CAS  Google Scholar 

  35. Feron O, Zhao Y-Y, Kelly RA. The ins and outs of caveolar signaling. m2 muscarinic cholinergic receptors and eNOS activation versus neuregulin and ErbB4 signaling in cardiac myocytes. Ann N Y Acad Sci. 1999;874:11–9.

    Article  PubMed  CAS  Google Scholar 

  36. Hazeki O, Ui M. Modification by islet-activating protein of receptor-mediated regulation of cyclic AMP accumulation in isolated rat heart cells. J Biol Chem. 1981;256:2856–62.

    PubMed  CAS  Google Scholar 

  37. Hescheler J, Kameyama M, Trautwein W. On the mechanism of muscarinic inhibition of the cardiac Ca current. Pflugers Arch. 1986;407:182–9.

    Article  PubMed  CAS  Google Scholar 

  38. Warrier S, Belevych AE, Ruse M, Eckert RL, Zaccolo M, Pozzan T, et al. β-Adrenergic- and muscarinic receptor-induced changes in cAMP activity in adult cardiac myocytes detected with FRET-based biosensor. Am J Physiol Cell Physiol. 2005;289:C455–61.

    Article  PubMed  CAS  Google Scholar 

  39. Feron O, Smith TW, Michel T, Kelly RA. Dynamic targeting of the agonist-stimulated m2 muscarinic acetylcholine receptor to caveolae in cardiac myocytes. J Biol Chem. 1997;272:17744–8.

    Article  PubMed  CAS  Google Scholar 

  40. Herzig S, Meier A, Pfeiffer M, Neumann J. Stimulation of protein phosphatases as a mechanism of the muscarinic-receptor-mediated inhibition of cardiac L-type Ca2+ channels. Pflugers Arch. 1995;429:531–8.

    Article  PubMed  CAS  Google Scholar 

  41. Shen JB, Pappano AJ. On the role of phosphatase in regulation of cardiac L-type calcium current by cyclic GMP. J Pharmacol Exp Ther. 2002;301:501–6.

    Article  PubMed  CAS  Google Scholar 

  42. Shi W, Wymore R, Yu H, Wu J, Wymore RT, Pan Z, et al. Distribution and prevalence of hyperpolarization activated cation channel (HCN) mRNA expression in cardiac tissues. Circ Res. 1999;85:e1–6.

    PubMed  CAS  Google Scholar 

  43. Ludwig A, Budde T, Stieber J, Moosmang S, Wahl C, Holthoff K, et al. Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2. EMBO J. 2003;22:216–24.

    Article  PubMed  CAS  Google Scholar 

  44. DiFrancesco D, Tortora P. Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature. 1991;351:145–7.

    Article  PubMed  CAS  Google Scholar 

  45. DiFrancesco D, Tromba C. Muscarinic control of the hyperpolarization-activated current (i f) in rabbit sino-atrial node myocytes. J Physiol. 1988;405:493–510.

    PubMed  CAS  Google Scholar 

  46. Hutter OF, Trautwein W. Vagal and sympathetic effects on the pacemaker fibers in the sinus venosus of the heart. J Gen Physiol. 1955;39:715–33.

    Article  Google Scholar 

  47. Yamada M, Inanobe A, Kurachi Y. G Protein regulation of potassium ion channels. Pharmacol Rev. 1998;50:723–57.

    PubMed  CAS  Google Scholar 

  48. Krapivinsky G, Gordon EA, Wickman K, Velimirovic B, Krapivinsky L, Clapham DE. The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+ channel protein. Nature. 1995;374:135–41.

    Article  PubMed  CAS  Google Scholar 

  49. Tucker SJ, Pessia M, Adelman JP. Muscarine-gated K+ channel: subunit stoichiometry and structural domains essential for G protein stimulation. Am J Physiol. 1996;271:H379–85.

    PubMed  CAS  Google Scholar 

  50. Reuveny E, Slesinger PA, Inglese J, Molales JM, Iniguez-Lluhi JA, Lefkowitz RJ, et al. Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits. Nature. 1994;370:143–6.

    Article  PubMed  CAS  Google Scholar 

  51. Slesinger PA, Reuveny E, Jan YN, Jan LY. Identification of structural elements involved in G protein gating of the GIRK1 potassium channel. Neuron. 1995;15:1145–56.

    Article  PubMed  CAS  Google Scholar 

  52. Dascal N, Doupnik CA, Ivanina T, Bausch S, Wang W, Lin C, et al. Inhibition of function in Xenopus oocytes of the inwardly rectifying G-protein-activated atrial K channel (GIRK1) by overexpression of a membrane-attached form of the C-terminal tail. Proc Natl Acad Sci USA. 1995;92:6758–62.

    Article  PubMed  CAS  Google Scholar 

  53. Huang C-L, Feng S, Hilgemann DW. Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ. Nature. 1998;391:803–6.

    Article  PubMed  CAS  Google Scholar 

  54. Wickman KD, Iniguez-Lluhi JA, Davenport PA, Taussig R, Krapivinsky GB, Linder ME, et al. Recombinant Gβγ activates the muscarinic-gated atrial potassium channel IKACh. Nature. 1994;368:255–7.

    Article  PubMed  CAS  Google Scholar 

  55. Doupnik CA, Davidson N, Lester HA, Kofuji P. RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K1 channels. Proc Natl Acad Sci USA. 1997;94:10461–6.

    Article  PubMed  CAS  Google Scholar 

  56. Verma SC, McNeill JH. Cardiac histamine receptors: differences between left and right atria and right ventricle. J Pharmacol Exp Ther. 1977;200:352–62.

    PubMed  CAS  Google Scholar 

  57. Arrang JM, Garbarg M, Schwartz JC. Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature. 1983;302:832–7.

    Article  PubMed  CAS  Google Scholar 

  58. Olsson RA, Pearson JD. Cardiovascular purinoceptors. Physiol Rev. 1990;70:761–845.

    PubMed  CAS  Google Scholar 

  59. Villalon CM, Centurion D. Cardiovascular responses produced by 5-hydroxytriptamine: a pharmacological update on the receptors/mechanisms involved and therapeutic implications. Naunyn Schmiedebergs Arch Pharmacol. 2007;376:45–63.

    Article  PubMed  CAS  Google Scholar 

  60. Yusuf S, Al-Saady N, Camm AJ. 5-Hydroxytryptamine and atrial fibrillation: how significant is this piece in the puzzle? J Cardiovasc Electrophysiol. 2003;14:209–14.

    Article  PubMed  Google Scholar 

  61. Ramage AG. Central cardiovascular regulation and 5-hydroxytryptamine receptors. Brain Res Bull. 2001;56:425–39.

    Article  PubMed  CAS  Google Scholar 

  62. Brattelid T, Qvigstad E, Lynham JA, Molenaar P, Aass H, Geiran O, et al. Functional serotonin 5-HT4 receptors in porcine and human ventricular myocardium with increased 5-HT4 mRNA in heart failure. Naunyn Schmiedebergs Arch Pharmacol. 2004;370:157–66.

    Article  PubMed  CAS  Google Scholar 

  63. Qvigstad E, Brattelid T, Sjaastad I, Andressen KW, Krobert KA, Birkeland JA, et al. Appearance of a ventricular 5-HT4 receptor-mediated inotropic response to serotonin in heart failure. Cardiovasc Res. 2005;65:869–78.

    Article  PubMed  CAS  Google Scholar 

  64. Saxena PR, Villalon CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol. 1990;15 Suppl 7:S17–34.

    PubMed  CAS  Google Scholar 

  65. Weihe E, Reinecke M. Peptidergic innervation of the mammalian sinus nodes: vasoactive intestinal polypeptide, neurotensin, substance P. Neurosci Lett. 1981;26:283–8.

    Article  PubMed  CAS  Google Scholar 

  66. Hokfelt T, Elfvin LG, Elde R, Schultzberg M, Goldstein M, Luft R. Occurrence of somatostatin-like immunoreactivity in some peripheral sympathetic noradrenergic neurons. Proc Natl Acad Sci USA. 1977;74:3587–91.

    Article  PubMed  CAS  Google Scholar 

  67. Jacques D, Sader S, Perreault C, Fournier A, Pelletier G, Beck-Sickinger AG, et al. Presence of neuropeptide Y and the Y1 receptor in the plasma membrane and nuclear envelope of human endocardial endothelial cells: modulation of intracellular calcium. Can J Physiol Pharmacol. 2003;81:288–300.

    Article  PubMed  CAS  Google Scholar 

  68. Jacques D, Abdel-Samad D. Neuropeptide Y (NPY) and NPY receptors in the cardiovascular system: implication in the regulation of intracellular calcium. Can J Physiol Pharmacol. 2007;85:43–53.

    Article  PubMed  CAS  Google Scholar 

  69. Balasubramaniam A, Grupp I, Matlib MA, Benza R, Jackson RL, Fischer JE, et al. Comparison of the effects of neuropeptide Y (NPY) and 4-norleucine-NPY on isolated perfused rat hearts; effects of NPY on atrial and ventricular strips of rat heart and on rabbit heart mitochondria. Regul Pept. 1988;21:289–99.

    Article  PubMed  CAS  Google Scholar 

  70. Wei Y, Mojsov S. Tissue specific expression of different human receptor types for pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide: implications for their role in human physiology. J Neuroendocrinol. 1996;8:811–7.

    Article  PubMed  CAS  Google Scholar 

  71. Chatelain P, Robberecht P, Waelbroeck M, De Neef P, Camus JC, Huu AN, et al. Topographical distribution of the secretin- and VIP-stimulated adenylate cyclase system in the heart of five animal species. Pflugers Arch. 1983;397:100–5.

    Article  PubMed  CAS  Google Scholar 

  72. Bell D, McDermott BJ. Secretin and vasoactive intestinal peptide are potent stimulants of cellular contraction and accumulation of cyclic AMP in rat ventricular cardiomyocytes. J Cardiovasc Pharmacol. 1994;23:959–69.

    Article  PubMed  CAS  Google Scholar 

  73. Accili EA, Redaelli G, DiFrancesco D. Activation of the hyperpolarization-activated current (if) in sino-atrial node myocytes of the rabbit by vasoactive intestinal peptide. Pflugers Arch. 1996;431:803–5.

    PubMed  CAS  Google Scholar 

  74. Pelaprat D. Interactions between neurotensin receptors and G proteins. Peptides. 2006;27:2476–87.

    Article  PubMed  CAS  Google Scholar 

  75. Osadchii O, Norton G, Deftereos D, Muller D, Woodiwiss A. Impact of chronic β-adrenoceptor activation on neurotensin-induced myocardial effects in rats. Eur J Pharmacol. 2006;553:246–53.

    Article  PubMed  CAS  Google Scholar 

  76. Siehler S, Hoyer D. Characterization of human recombinant somatostatin receptors: modulation of adenylate cyclase activity. Naunyn Schmiedebergs Arch Pharmacol. 1999;360:510–21.

    Article  PubMed  CAS  Google Scholar 

  77. Tallent M, Liapakis G, O’Carroll AM, Lolait SJ, Dichter M, Reisine T. Somatostatin receptor subtypes SSTR2 and SSTR5 couple negatively to an L type calcium channel current in the pituitary cell line AtT-20. Neuroscience. 1996;71:1073–81.

    Article  PubMed  CAS  Google Scholar 

  78. Kreienkamp HJ, Honck HH, Richter D. Coupling of rat somatostatin receptor subtypes to a G-protein gated inwardly rectifying potassium channel. FEBS Lett. 1997;419:92–4.

    Article  PubMed  CAS  Google Scholar 

  79. Akbar M, Okajima F, Tomura H, Majid MA, Yamada Y, Seino S, et al. Phospholipase C activation and calcium mobilization by cloned human somatostatin receptor subtypes 1–5 in transfected cos-7 cells. FEBS Lett. 1994;348:192–6.

    Article  PubMed  CAS  Google Scholar 

  80. Bell D, Zhao Y, McMaster B, McHenry EM, Wang X, Kelso EJ, et al. SRIF receptor subtype expression and involvement in positive and negative contractile effects of somatostatin-14 (SRIF-14) in ventricular cardiomyocytes. Cell Physiol Biochem. 2008;22:653–64.

    Article  PubMed  CAS  Google Scholar 

  81. Schwabe W, Brennan MB, Hochgeschwender U. Isolation and characterization of the mouse (Mus musculus) somatostatin receptor type 4-encoding gene (mSSTR4). Gene. 1996;168:233–5.

    Article  PubMed  CAS  Google Scholar 

  82. Smith WHT, Nair RU, Adamson D, Kearney MT, Ball SG, Balmforth AJ. Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts. J Endocrinol. 2005;187:379–86.

    Article  PubMed  CAS  Google Scholar 

  83. Murray F, Bell D, Kelso EJ, Millar BC, McDermott BJ. Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes. J Cardiovasc Pharmacol. 2001;37:324–32.

    Article  PubMed  CAS  Google Scholar 

  84. Boehm S, Huck S. Receptors controlling transmitter release from sympathetic neurons in vitro. Prog Neurobiol. 1997;51:225–42.

    Article  PubMed  CAS  Google Scholar 

  85. Endoh M, Murayama M, Taira N. Modification by islet-activating protein of direct and indirect inhibitory actions of adenosine on rat atrial contraction in relation to cyclic nucleotide metabolism. J Cardiovasc Pharmacol. 1983;5:131–42.

    Article  PubMed  CAS  Google Scholar 

  86. Leung E, Johnston CI, Woodcock EA. A comparison between the adenosine receptors mediating adenylate cyclase inhibition and cardiac depression in the guinea pig heart. J Cardiovasc Pharmacol. 1986;8:1003–8.

    Article  PubMed  CAS  Google Scholar 

  87. Chiba S, Himori N. Different inotropic responses to adenosine on the atria1 and ventricular muscle of the dog heart. Jpn J Pharmacol. 1975;25:489–91.

    Article  PubMed  CAS  Google Scholar 

  88. Kubalak SW, Newman W, Webb JG. Differential effect of pertussis toxin on adenosine and muscarinic inhibition of cyclic AMP accumulation in canine ventricular myocytes. J Mol Cell Cardiol. 1991;23:199–205.

    Article  PubMed  CAS  Google Scholar 

  89. Trautwein W, Cavalie A, Flockerzei V, Hofmann F, Pelzer D. Modulation of calcium channel function by phosphorylation in guinea pig ventricular cells and phospholipids bilayer membranes. Circ Res. 1987;61(Suppl I):I-17–23.

    CAS  Google Scholar 

  90. Walsh KB, Kass RS. Regulation of a heart potassium channel by protein kinase A and C. Science. 1988;242:67–9.

    Article  PubMed  CAS  Google Scholar 

  91. Martynyuk AG, Kane KA, Cobbe SM, Rankin AC. Nitric oxide mediates the anti-adrenergic effect of adenosine on calcium current in isolated rabbit atrioventricular nodal cells. Pflugers Arch. 1996;431:452–7.

    Article  PubMed  CAS  Google Scholar 

  92. Hove-Madsen L, Prat-Vidal C, Llach A, Ciruela F, Casado V, Lluis C, et al. Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release. Cardiovasc Res. 2006;72:292–302.

    Article  PubMed  CAS  Google Scholar 

  93. Xu H, Stein B, Liang B. Characterization of a stimulatory adenosine A2a receptor in adult rat ventricular myocyte. Am J Physiol. 1996;270:H16550–61.

    Google Scholar 

  94. Richardt G, Waas W, Kranzhofer R, Mayer E, Schomig A. Adenosine inhibits exocytotic release of endogenous noradrenaline in rat heart: a protective mechanism in early myocardial ischemia. Circ Res. 1987;61:117–23.

    PubMed  CAS  Google Scholar 

  95. Thomas WG, Thekkumkara TJ, Baker KM. Cardiac effects of AIIAT1A receptor signaling, desensitization, and internalization. Adv Exp Med Biol. 1996;396:59–69.

    PubMed  CAS  Google Scholar 

  96. Nio Y, Matsubara H, Murasawa S, Kanasaki M, Inada M. Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J Clin Invest. 1995;95:46–54.

    Article  PubMed  CAS  Google Scholar 

  97. Ono K, Eto K, Sakamoto A, Masaki T, Shibata K, Sada T, et al. Negative chronotropic effect of endothelin 1 mediated through ETA receptors in guinea pig atria. Circ Res. 1995;76:284–92.

    PubMed  CAS  Google Scholar 

  98. Humbert M, Simonneau G. Drug insight: endothelin-receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases. Nat Clin Pract Rheumatol. 2005;1:93–101.

    Article  PubMed  CAS  Google Scholar 

  99. McGoon MD, Frost AE, Oudiz RJ, Badesch DB, Galie N, Olschewski H, et al. Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities. Chest. 2009;135:122–9.

    Article  PubMed  CAS  Google Scholar 

  100. Ng LL, Loke IW, O’Brien RJ, Squire IB, Davies JE. Plasma urocortin in human systolic heart failure. Clin Sci (Lond). 2004;106:383–8.

    Article  CAS  Google Scholar 

  101. Dibb KM, Graham HK, Venetucci LA, Eisner DA, Trafford AW. Analysis of cellular calcium fluxes in cardiac muscle to understand calcium homeostasis in the heart. Cell Calcium. 2007;42:503–12.

    Article  PubMed  CAS  Google Scholar 

  102. Quednau BD, Nicoll DA, Philipson KD. Tissue specificity and alternative splicing of the Na+/Ca2+ exchanger isoforms NCX1, NCX2, and NCX3 in rat. Am J Physiol. 1997;272:C1250–61.

    PubMed  CAS  Google Scholar 

  103. Sasaki N, Mitsuiye T, Noma A. Effects of mechanical stretch on membrane currents of single ventricular myocytes of guinea-pig heart. Jpn J Physiol. 1992;42:957–70.

    Article  PubMed  CAS  Google Scholar 

  104. Coulombe A, Lefever IA, Baro I, Coraboeuf E. Barium- and calcium-permeable channels open at negative membrane potentials in rat ventricular myocytes. J Membr Biol. 1989;111:57–67.

    Article  PubMed  CAS  Google Scholar 

  105. Uehara A, Yasukochi M, Imanaga I, Nishi M, Takeshima H. Store-operated Ca2+ entry uncoupled with ryanodine receptor and junctional membrane complex in heart muscle cells. Cell Calcium. 2002;31:89–96.

    Article  PubMed  CAS  Google Scholar 

  106. Satoh S, Tanaka H, Ueda Y, Oyama J, Sugano M, Sumimoto H, et al. Transient receptor potential (TRP) protein 7 acts as a G protein-activated Ca2+ channel mediating angiotensin II-induced myocardial apoptosis. Mol Cell Biochem. 2007;294:205–15.

    Article  PubMed  CAS  Google Scholar 

  107. Asahi M, Nakayama H, Tada M, Otsu K. Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin: implication for cardiac hypertrophy and failure. Trends Cardiovasc Med. 2003;13:152–7.

    Article  PubMed  CAS  Google Scholar 

  108. Cartwright EJ, Schuh K, Neyses L. Calcium transport in cardiovascular health and disease – the sarcolemmal calcium pump enters the stage. J Mol Cell Cardiol. 2005;39:403–6.

    Article  PubMed  CAS  Google Scholar 

  109. Kockskämper J, Zima AV, Roderick HL, Pieske B, Blatter LA, Bootman MD. Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes. J Mol Cell Cardiol. 2008;45:128–47.

    Article  PubMed  CAS  Google Scholar 

  110. Sasse P, Zhang J, Cleemann L, Morad M, Hescheler J, Fleischmann BK. Intracellular Ca2+ oscillations, a potential pacemaking mechanism in early embryonic heart cells. J Gen Physiol. 2007;130:133–44.

    Article  PubMed  CAS  Google Scholar 

  111. Zima AV, Bare DJ, Mignery GA, Blatter LA. IP3-dependent nuclear Ca2+ signalling in the mammalian heart. J Physiol. 2007;584:601–11.

    Article  PubMed  CAS  Google Scholar 

  112. Wu X, Zhang T, Bossuyt J, Li X, McKinsey TA, Dedman JR, et al. Local InsP3-dependent perinuclear Ca2+ signaling in cardiac myocyte excitation-transcription coupling. J Clin Invest. 2006;116:675–82.

    Article  PubMed  CAS  Google Scholar 

  113. Carafoli E. Historical review: mitochondria and calcium: ups and downs of an unusual relationship. Trends Biochem Sci. 2003;28:175–81.

    Article  PubMed  CAS  Google Scholar 

  114. Bell CJ, Bright NA, Rutter GA, Griffiths EJ. ATP regulation in adult rat cardiomyocytes: time-resolved decoding of rapid mitochondrial calcium spiking imaged with targeted photoproteins. J Biol Chem. 2006;281:28058–67.

    Article  PubMed  CAS  Google Scholar 

  115. Beutner G, Sharma VK, Lin L, Ryu SY, Dirksen RT, Sheu SS. Type 1 ryanodine receptor in cardiac mitochondria: transducer of excitation–metabolism coupling. Biochim Biophys Acta. 2005;1717:1–10.

    Article  PubMed  CAS  Google Scholar 

  116. Jo H, Noma A, Matsuoka S. Calcium-mediated coupling between mitochondrial substrate dehydrogenation and cardiac workload in single guinea-pig ventricular myocytes. J Mol Cell Cardiol. 2006;40:394–404.

    Article  PubMed  CAS  Google Scholar 

  117. Balaban RS. The role of Ca2+ signaling in the coordination of mitochondrial ATP production with cardiac work. Biochim Biophys Acta. 2009;1787:1334–41.

    Article  PubMed  CAS  Google Scholar 

  118. Denton RM. Regulation of mitochondrial dehydrogenases by calcium ions. Biochim Biophys Acta. 2009;1787:1309–16.

    Article  PubMed  CAS  Google Scholar 

  119. Hopper RK, Carroll S, Aponte AM, Johnson DT, French S, Shen RF, et al. Mitochondrial matrix phosphoproteome: effect of extra mitochondrial calcium. Biochemistry. 2006;45:2524.

    Article  PubMed  CAS  Google Scholar 

  120. Yamada EW, Huzel NJ. The calcium binding ATPase inhibitor protein from bovine heart mitochondria. Purification and properties. J Biol Chem. 1988;263:11498.

    PubMed  CAS  Google Scholar 

  121. Boerries M, Most P, Gledhill JR, Walker JE, Katus HA, Koch WJ, et al. Ca2+-dependent interaction of S100A1 with F1-ATPase leads to an increased ATP content in cardiomyocytes. Mol Cell Biol. 2007;27:4365.

    Article  PubMed  CAS  Google Scholar 

  122. Garcia-Perez C, Hajnoczky G, Csordas G. Physical coupling supports the local Ca2+ transfer between SR subdomains and the mitochondria in heart muscle. J Biol Chem. 2008;283:32771–80.

    Article  PubMed  CAS  Google Scholar 

  123. Sanchez JA, Garcia MC, Sharma VK, Young KC, Matlib MA, Sheu S-S. Mitochondria regulate inactivation of L-type Ca2+ channels in rat heart. J Physiol. 2001;536:387–96.

    Article  PubMed  CAS  Google Scholar 

  124. Metzger JM, Westfall MV. Covalent and noncovalent modification of thin filament action. The essential role of troponin in cardiac muscle regulation. Circ Res. 2004;94:146–58.

    Article  PubMed  CAS  Google Scholar 

  125. Kabaeva ZT, Perrot A, Wolter B, Dietz R, Cardim N, Correia JM, et al. Systematic analysis of the regulatory and essential myosin light chain genes: genetic variants and mutations in hypertrophic cardiomyopathy. Eur J Hum Genet. 2002;10:741–8.

    Article  PubMed  CAS  Google Scholar 

  126. Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS. Calcium-dependent and -independent interactions of the S100 protein family. Biochem J. 2006;396:201–14.

    Article  PubMed  CAS  Google Scholar 

  127. Most P, Remppis A, Pleger ST, Katus HA, Koch WJ. S100A1: a novel inotropic regulator of cardiac performance. Transition from molecular physiology to pathophysiological relevance. Am J Physiol Regul Integr Comp Physiol. 2007;293:R568–77.

    Article  PubMed  CAS  Google Scholar 

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Marín-García, J. (2011). Rapid Signaling Pathways. In: Signaling in the Heart. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9461-5_4

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