Abstract
The ryanodine receptors (RyRs) is the major intracellular Ca2+ release channel localized in the plasma membrane of the endoplasmatic/sarcoplasmatic reticulum. RyR-mediated Ca2+ release is crucial for every heart beat and skeletal muscle contraction and also important in learning and memory. Given the important role RyR has in physiological functions it is not surprising that dysregulation and impaired RyR channel function contributes to severe pathologies e.g. cardiac arrhythmias and Alzheimer’s disease. Mutations in the RyR channels are associated with a number of human disorders e.g. malignant hyperthermia (MH) and central core disease (CCD), catecholaminergic polymorphic ventricular tachycardia (CPVT), and arrhythmogenic right ventricular dysplasia (ARVD). RyRs are modulated directly and indirectly by various ions, small molecules and proteins and RyR structure and function are expected to be defined within this macromolecular set of interactions. This article discusses the physiological function of RyR and examines its role in disorders and diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Rizzuto R, Pozzan T (2006) Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev 86:369–408
Sudhof TC (2002) Synaptotagmins: why so many? J Biol Chem 277:7629–7632
Berridge MJ, Bootman MD, Roderick LH (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4:517–529
Bootman MD, Lipp P, Berridge MJ (2001) The organisation and functions of local Ca2+ signals. J Cell Sci 114:2213–2222
Westerblad H, Lee JA, Lännergren J, Allen DG (1991) Cellular mechanisms of fatigue in skeletal muscle. Am J Physiol 261:C195–C209
Ozil JP, Swann K (1995) Stimulation of repetitive calcium transients in mouse eggs. J Physiol 483:331–346
Lewis RS (2001) Calcium signaling mechanisms in T lymphocytes. Annu Rev Immunol 19:497–521
Dolmetsch RE, Xu K, Lewis RS (1998) Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392:933–936
Smyth JT, Hwang S-Y, Tomita T, DeHaven WI, Mercer JC, Putney JW (2010) Activation and regulation of store-operated calcium entry. J Cell Mol Med 14:2337–2349
Inui M, Saito A, Fleischer S (1987) Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. J Biol Chem 262:1740–1747
Takeshima H, Nishimura S, Matsumoto T, Ishida H, Kangawa K, Minamino N, Matsuo H, Ueda M, Hanaoka M, Hirose T et al (1989) Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature 339:439–445
Nakai J, Imagawa T, Hakamat Y, Shigekawa M, Takeshima H, Numa S (1990) Primary structure and functional expression from cDNA of the cardiac ryanodine receptor/calcium release channel. FEBS Lett 271:169–177
Otsu K, Willard HF, Khanna VK, Zorzato F, Green NM, MacLennan DH (1990) Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem 265:13472–13483
Zorzato F, Fujii J, Otsu K, Phillips M, Green NM, Lai FA, Meissner G, MacLennan DH (1990) Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J Biol Chem 265:2244–2256
Hakamata Y, Nakai J, Takeshima H, Imoto K (1992) Primary structure and distribution of a novel ryanodine receptor/calcium release channel from rabbit brain. FEBS Lett 312:229–235
Smith JS, Coronado R, Meissner G (1985) Sarcoplasmic reticulum contains adenine nucleotide-activated calcium channels. Nature 316:446–449
Smith J, Coronado R, Meissner G (1986) Single channel measurements of the calcium release channel from skeletal muscle sarcoplasmic reticulum: activation by Ca2+ and ATP and modulation by Mg2+. J Gen Physiol 88:573–588
Furuichi T, Furutama D, Hakamata Y, Nakai J, Takeshima H, Mikoshiba K (1994) Multiple types of ryanodine receptor/Ca2+ release channels are differentially expressed in rabbit brain. J Neurosci 14:4794–4805
Hertle DN, Yeckel MF (2007) Distribution of inositol-1,4,5-trisphosphate receptor isotypes and ryanodine receptor isotypes during maturation of the rat hippocampus. Neuroscience 150:625–638
Lai FA, Dent M, Wickenden C, Xu L, Kumari G, Misra M, Lee HB, Sar M, Meissner G (1992) Expression of a cardiac Ca2+-release channel isoform in mammalian brain. Biochem J 288:553–564
Futatsugi A, Kato K, Ogura H, Li S-T, Nagata E, Kuwajima G, Tanaka K, Itohara S, Mikoshiba K (1999) Facilitation of NMDAR-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3. Neuron 24:701–713
Marks AR, Tempst P, Hwang KS, Taubman MB, Inui M, Chadwick C, Fleischer S, Nadal-Ginard B (1989) Molecular cloning and characterization of the ryanodine receptor/junctional channel complex cDNA from skeletal muscle sarcoplasmic reticulum. Proc Natl Acad Sci USA 86:8683–8687
Lanner JT, Georgiou DK, Joshi AD, Hamilton SL (2010) Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2:a003996
Meissner G (1986) Ryanodine activation and inhibition of the Ca2+ release channel of sarcoplasmic reticulum. J Biol Chem 261:6300–6306
Meissner G (1994) Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. Annu Rev Physiol 56:485–508
Meissner G, Rios E, Tripathy A, Pasek DA (1997) Regulation of skeletal muscle Ca2+ release channel (ryanodine receptor) by Ca2+ and monovalent cations and anions. J Biol Chem 272:1628–1638
Györke I, Györke S (1998) Regulation of the cardiac ryanodine receptor channel by luminal Ca2+ involves luminal Ca2+ sensing sites. Biophys J 75:2801–2810
Melzer W, Herrmann-Frank A, Lüttgau HC (1995) The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibres. Biochim Biophys Acta 1241:59–116
Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415:198–205
Dulhunty AF (1992) The voltage-activation of contraction in skeletal muscle. Prog Biophys Mol Biol 57:181–223
Franzini-Armstrong C (1991) Simultaneous maturation of transverse tubules and sarcoplasmic reticulum during muscle differentiation in the mouse. Dev Biol 146:353–363
Franzini-Armstrong C, Jorgensen AO (1994) Structure and development of E-C coupling units in skeletal muscle. Annu Rev Physiol 56:509–534
Carafoli E (1987) Intracellular calcium homeostasis. Annu Rev Biochem 56:395–433
Maclennan DH, Abu-Abed M, Kang C (2002) Structure-function relationships in Ca2+ cycling proteins. J Mol Cell Cardiol 34:897–918
Stephenson DG, Lamb GD, Stephenson GM (1998) Events of the excitation-contraction-relaxation (E-C-R) cycle in fast- and slow-twitch mammalian muscle fibres relevant to muscle fatigue. Acta Physiol Scand 162:229–245
Campbell DT (1983) Sodium channel gating currents in frog skeletal muscle. J Gen Physiol 82:679–701
Denborough M (1998) Malignant hyperthermia. Lancet 352:1131–1136
Lehnart SE, Mongillo M, Bellinger A, Lindegger N, Chen B-X, Hsueh W, Reiken S, Wronska A, Drew LJ, Ward CW, Lederer WJ, Kass RS, Morley G, Marks AR (2008) Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice. J Clin Invest 118:2230–2245
Bellinger AM, Reiken S, Dura M, Murphy PW, Deng S-X, Landry DW, Nieman D, Lehnart SE, Samaru M, LaCampagne A, Marks AR (2008) Remodeling of ryanodine receptor complex causes “leaky” channels: a molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci USA 105:2198–2202
Bellinger AM, Reiken S, Carlson C, Mongillo M, Liu X, Rothman L, Matecki S, Lacampagne A, Marks AR (2009) Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat Med 15:325–330
Durham WJ, Aracena-Parks P, Long C, Rossi AE, Goonasekera SA, Boncompagni S, Galvan DL, Gilman CP, Baker MR, Shirokova N, Protasi F, Dirksen R, Hamilton SL (2008) RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice. Cell 133:53–65
Ferdinandy P, Schulz R (2003) Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning. Br J Pharmacol 138:532–543
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 101:365–376
Reiken S, Lacampagne A, Zhou H, Kherani A, Lehnart SE, Ward C, Huang F, Gaburjakova M, Gaburjakova J, Rosemblit N, Warren MS, He K-l, Yi G-h, Wang J, Burkhoff D, Vassort G, Marks AR (2003) PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure. J Cell Biol 160:919–928
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) FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 113:829–840
Ai X, Curran JW, Shannon TR, Bers DM, Pogwizd SM (2005) Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. Circ Res 97:1314–1322
Chelu MG, Sarma S, Sood S, Wang S, van Oort RJ, Skapura DG, Li N, Santonastasi M, Muller FU, Schmitz W, Schotten U, Anderson ME, Valderrabano M, Dobrev D, Wehrens XHT (2009) Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice. J Clin Invest 119:1940–1951
Neef S, Dybkova N, Sossalla S, Ort KR, Fluschnik N, Neumann K, Seipelt R, Schondube FA, Hasenfuss G, Maier LS (2010) CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation. Circ Res 106:1134–1144
Curran J, Brown KH, Santiago DJ, Pogwizd S, Bers DM, Shannon TR (2010) Spontaneous Ca waves in ventricular myocytes from failing hearts depend on Ca2+-calmodulin-dependent protein kinase II. J Mol Cell Cardiol 49:25–32
Liu N, Ruan Y, Denegri M, Bachetti T, Li Y, Colombi B, Napolitano C, Coetzee WA, Priori SG (2011) Calmodulin kinase II inhibition prevents arrhythmias in RyR2R4496C+/− mice with catecholaminergic polymorphic ventricular tachycardia. J Mol Cell Cardiol 50:214–222
Kashimura T, Briston SJ, Trafford AW, Napolitano C, Priori SG, Eisner DA, Venetucci LA (2010) In the RyR2R4496C+/− mouse model of CPVT, β-adrenergic stimulation induces Ca2+ waves by increasing SR Ca2+ content and not by decreasing the threshold for Ca2+ waves. Circ Res 107:1483–1489
Jiang D, Xiao B, Zhang L, Chen SR (2002) Enhanced basal activity of a cardiac Ca2+ release channel (ryanodine receptor) mutant associated with ventricular tachycardia and sudden death. Circ Res 91:218–225
Chelu MG, Danila CI, Gilman CP, Hamilton SL (2004) Regulation of ryanodine receptors by FK506 binding proteins. Trends Cardiovasc Med 14:227–234
Brillantes AB, Ondrias K, Scott A, Kobrinsky E, Ondriasova E, Moschella MC, Jayaraman T, Landers M, Ehrlich BE, Marks AR (1994) Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein. Cell 77:513–523
Jayaraman T, Brillantes AM, Timerman AP, Fleischer S, Erdjument-Bromage H, Tempst P, Marks AR (1992) FK506 binding protein associated with the calcium release channel (ryanodine receptor). J Biol Chem 267:9474–9477
Timerman AP, Onoue H, Xin H-B, Barg S, Copello J, Wiederrecht G, Fleischer S (1996) Selective binding of FKBP12.6 by the cardiac ryanodine receptor. J Biol Chem 271:20385–20391
Timerman AP, Ogunbumni E, Freund E, Wiederrecht G, Marks AR, Fleischer S (1993) The calcium release channel of sarcoplasmic reticulum is modulated by FK-506-binding protein. Dissociation and reconstitution of FKBP-12 to the calcium release channel of skeletal muscle sarcoplasmic reticulum. J Biol Chem 268:22992–22999
Qi Y, Ogunbunmi EM, Freund EA, Timerman AP, Fleischer S (1998) FK-binding protein is associated with the ryanodine receptor of skeletal muscle in vertebrate animals. J Biol Chem 273:34813–34819
Marx SO, Ondrias K, Marks AR (1998) Coupled gating between individual skeletal muscle Ca2+ release channels (Ryanodine Receptors). Science 281:818–821
Eager KR, Dulhunty AF (1998) Activation of the cardiac ryanodine receptor by sulfhydryl oxidation is modified by Mg2+ and ATP. J Membr Biol 163:9–18
Stoyanovsky D, Murphy T, Anno PR, Kim YM, Salama G (1997) Nitric oxide activates skeletal and cardiac ryanodine receptors. Cell Calcium 21:19–29
Zable AC, Favero TG, Abramson JJ (1997) Glutathione modulates ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Evidence for redox regulation of the Ca2+ release mechanism. J Biol Chem 272:7069–7077
Xu L, Eu JP, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234–237
Bouchama A, Knochel JP (2002) Heat Stroke. N Engl J Med 346:1978–1988
Hopkins PM, Ellis FR, Halsall PJ (1991) Evidence for related myopathies in exertional heat stroke and malignant hyperthermia. Lancet 338:1491–1492
Capacchione JF, Muldoon SM (2009) The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia. Anesth Analg 109:1065–1069
Rosenberg H, Davis M, James D, Pollock N, Stowell K (2007) Malignant hyperthermia. Orphanet J Rare Dis 2:21
Jurkat-Rott K, McCarthy T, Lehmann-Horn F (2000) Genetics and pathogenesis of malignant hyperthermia. Muscle Nerve 23:4–17
Pamukcoglu T (1988) Sudden death due to malignant hyperthermia. Am J Forensic Med Pathol 9:161–162
Ryan JF, Tedeschi LG (1997) Sudden unexplained death in a patient with a family history of malignant hyperthermia. J Clin Anesth 9:66–68
Tong J, McCarthy TV, MacLennan DH (1999) Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels. J Biol Chem 274:693–702
Brandom BW, Larach MG, Chen MSA, Young MC (2011) Complications associated with the administration of dantrolene 1987 to 2006: a report from the North American malignant hyperthermia registry of the malignant hyperthermia association of the United States. Anesth Analg 112:1115–1123
Krause T, Gerbershagen MU, Fiege M, Weishorn R, Wappler F (2004) Dantrolene – a review of its pharmacology, therapeutic use and new developments. Anaesthesia 59:364–373
Ward A, Chaffman MO, Sorkin EM (1986) Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. Drugs 32:130–168
Palnitkar SS, Bin B, Jimenez LS, Morimoto H, Williams PG, Paul-Pletzer K, Parness J (1999) [3 H]Azidodantrolene: synthesis and use in identification of a putative skeletal muscle dantrolene binding site in sarcoplasmic reticulum. J Med Chem 42:1872–1880
Parness J, Palnitkar SS (1995) Identification of dantrolene binding sites in porcine skeletal muscle sarcoplasmic reticulum. J Biol Chem 270:18465–18472
Jungbluth H (2007) Central core disease. Orphanet J Rare Dis 2:25
Jungbluth H (2007) Multi-minicore disease. Orphanet J Rare Dis 2:31
Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P (2006) Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat 27:977–989
Robinson RL, Brooks C, Brown SL, Ellis FR, Halsall PJ, Quinnell RJ, Shaw M-A, Hopkins PM (2002) RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes. Hum Mutat 20:88–97
Jungbluth H, Müller CR, Halliger-Keller B, Brockington M, Brown SC, Feng L, Chattopadhyay A, Mercuri E, Manzur AY, Ferreiro A, Laing NG, Davis MR, Roper HP, Dubowitz V, Bydder G, Sewry CA, Muntoni F (2002) Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores. Neurology 59:284–287
Sewry CA, Müller C, Davis M, Dwyer JSM, Dove J, Evans G, Schröder R, Fürst D, Helliwell T, Laing N, Quinlivan RCM (2002) The spectrum of pathology in central core disease. Neuromuscul Disord 12:930–938
Zhang Y, Chen HS, Khanna VK, De Leon S, Phillips MS, Schappert K, Britt BA, Browell AK, MacLennan DH (1993) A mutation in the human ryanodine receptor gene associated with central core disease. Nat Genet 5:46–50
Dirksen RT, Avila G (2002) Altered ryanodine receptor function in central core disease: leaky or uncoupled Ca2+ release channels? Trends Cardiovasc Med 12:189–197
Quane KA, Healy JM, Keating KE, Manning BM, Couch FJ, Palmucci LM, Doriguzzi C, Fagerlund TH, Berg K, Ording H et al (1993) Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nat Genet 5:51–55
Avila G, Dirksen RT (2001) Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor. J Gen Physiol 118:277–290
Napolitano C, Priori SG (2007) Diagnosis and treatment of catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 4:675–678
Laitinen PJ, Swan H, Kontula K (2004) Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms. Eur J Hum Genet 11:888–891
Eldar M, Pras E, Lahat H (2003) A missense mutation in the CASQ2 gene is associated with autosomal-recessive catecholamine-induced polymorphic ventricular tachycardia. Trends Cardiovasc Med 13:148–151
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 103:196–200
Györke I, Hester N, Jones LR, Györke S (2004) The role of calsequestrin, triadin, and junctin in conferring cardiac ryanodine receptor responsiveness to luminal calcium. Biophys J 86:2121–2128
Terentyev D, Kubalova Z, Valle G, Nori A, Vedamoorthyrao S, Terentyeva R, Viatchenko-Karpinski S, Bers DM, Williams SC, Volpe P, Gyorke S (2008) Modulation of SR Ca release by luminal Ca and calsequestrin in cardiac myocytes: effects of CASQ2 mutations linked to sudden cardiac death. Biophys J 95:2037–2048
Hayashi M, Denjoy I, Extramiana F, Maltret A, Buisson NR, Lupoglazoff J-M, Klug D, Hayashi M, Takatsuki S, Villain E, Kamblock J, Messali A, Guicheney P, Lunardi J, Leenhardt A (2009) Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 119:2426–2434
Haugaa KH, Leren IS, Berge KE, Bathen J, Loennechen JP, Anfinsen O-G, Früh A, Edvardsen T, Kongsgård E, Leren TP, Amlie JP (2010) High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening. Europace 12:417–423
van der Werf C, Kannankeril PJ, Sacher F, Krahn AD, Viskin S, Leenhardt A, Shimizu W, Sumitomo N, Fish FA, Bhuiyan ZA, Willems AR, van der Veen MJ, Watanabe H, Laborderie J, Haïssaguerre M, Knollmann BC, Wilde AAM (2011) Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol 57:2244–2254
Watanabe H, Chopra N, Laver D, Hwang HS, Davies SS, Roach DE, Duff HJ, Roden DM, Wilde AAM, Knollmann BC (2009) Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med 15:380–383
Hwang HS, Hasdemir C, Laver D, Mehra D, Turhan K, Faggioni M, Yin H, Knollmann BC (2011) Inhibition of cardiac Ca2+ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol 4:128–135
De Rosa G, Delogu A, Piastra M, Chiaretti A, Bloise R, Priori S (2004) Cathecolaminergic polymorphic ventricular tachycardia: successful emergency treatment with intravenous propranolol. Pediatr Emerg Care 20:175–177
Marks AR, Priori S, Memmi M, Kontula K, Laitinen PJ (2002) Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia. J Cell Physiol 190:1–6
Kobayashi S, Yano M, Suetomi T, Ono M, Tateishi H, Mochizuki M, Xu X, Uchinoumi H, Okuda S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M (2009) Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor. J Am Coll Cardiol 53:1993–2005
Corrado D, Basso C, Thiene G (2000) Arrhythmogenic right ventricular cardiomyopathy: diagnosis, prognosis, and treatment. Heart 83:588–595
Muthappan P, Calkins H (2008) Arrhythmogenic right ventricular dysplasia. Prog Cardiovasc Dis 51:31–43
Gleissner CA, Galkina E, Nadler JL, Ley K (2007) Mechanisms by which diabetes increases cardiovascular disease. Drug Discov Today Dis Mech 4:131–140
Gu K, Cowie CC, Harris MI (1998) Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971–1993. Diabetes Care 21:1138–1145
Pereira L, Matthes J, Schuster I, Valdivia HH, Herzig S, Richard S, Gomez AM (2006) Mechanisms of [Ca2+]i transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes 55:608–615
Shao C-H, Rozanski GJ, Patel KP, Bidasee KR (2007) Dyssynchronous (non-uniform) Ca2+ release in myocytes from streptozotocin-induced diabetic rats. J Mol Cell Cardiol 42:234–246
Shao C-H, Wehrens XHT, Wyatt TA, Parbhu S, Rozanski GJ, Patel KP, Bidasee KR (2009) Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulation. J Appl Physiol 106:1280–1292
Tian C, Shao CH, Moore CJ, Kutty S, Walseth T, DeSouza C, Bidasee KR (2011) Gain of function of cardiac ryanodine receptor in a rat model of type 1 diabetes. Cardiovasc Res 91:300–309
Yaras N, Ugur M, Ozdemir S, Gurdal H, Purali N, Lacampagne A, Vassort G, Turan B (2005) Effects of diabetes on ryanodine receptor Ca2+ release channel (RyR2) and Ca2+ homeostasis in rat heart. Diabetes 54:3082–3088
Fauconnier J, Lanner JT, Zhang SJ, Tavi P, Bruton JD, Katz A, Westerblad H (2005) Insulin and inositol 1,4,5-trisphosphate trigger abnormal cytosolic Ca2+ transients and reveal mitochondrial Ca2+ handling defects in cardiomyocytes of ob/ob mice. Diabetes 54:2375–2381
Goussakov I, Chakroborty S, Stutzmann GE (2011) Generation of dendritic Ca2+ oscillations as a consequence of altered ryanodine receptor function in AD neurons. Channels (Austin) 5:9–13
Sajikumar S, Li Q, Abraham WC, Xiao ZC (2009) Priming of short-term potentiation and synaptic tagging/capture mechanisms by ryanodine receptor activation in rat hippocampal CA1. Learn Mem 16:178–186
Berridge M (2010) Calcium hypothesis of Alzheimer’s disease. Pflugers Arch 459:441–449
Stutzmann GE, Caccamo A, LaFerla FM, Parker I (2004) Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer’s-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci 24:508–513
Guo Q, Fu W, Sopher BL, Miller MW, Ware CB, Martin GM, Mattson MP (1999) Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice. Nat Med 5:101–106
Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631–639
Chakroborty S, Goussakov I, Miller MB, Stutzmann GE (2009) Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. J Neurosci 29:9458–9470
Goussakov I, Miller MB, Stutzmann GE (2010) NMDA-mediated Ca2+ influx drives aberrant ryanodine receptor activation in dendrites of young Alzheimer’s disease mice. J Neurosci 30:12128–12137
Stutzmann GE, Smith I, Caccamo A, Oddo S, LaFerla FM, Parker I (2006) Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer’s disease mice. J Neurosci 26:5180–5189
Lopez JR, Lyckman A, Oddo S, LaFerla FM, Querfurth HW, Shtifman A (2008) Increased intraneuronal resting [Ca2+] in adult Alzheimer’s disease mice. J Neurochem 105:262–271
Ruiz A, Matute C, Alberdi E (2010) Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes. Cell Death Dis 1:e54
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Lanner, J.T. (2012). Ryanodine Receptor Physiology and Its Role in Disease. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 740. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2888-2_9
Download citation
DOI: https://doi.org/10.1007/978-94-007-2888-2_9
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-2887-5
Online ISBN: 978-94-007-2888-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)