Skip to main content
SpringerLink
Log in

Functional interaction between calsequestrin and ryanodine receptor in the heart

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Evidence obtained in the last two decades indicates that calsequestrin (CSQ2), as the major Ca2+-binding protein in the sarcoplasmic reticulum of cardiac myocytes, communicates changes in the luminal Ca2+ concentration to the cardiac ryanodine receptor (RYR2) channel. This review summarizes the major aspects in the interaction between CSQ2 and the RYR2 channel. The single channel properties of RYR2 channels, discussed here in the context of structural changes in CSQ2 after Ca2+ binding, are particularly important. We focus on five important questions concerning: (1) the method for reliable detection of CSQ2 on the reconstituted RYR2 channel complex; (2) the power of the procedure to strip CSQ2 from the RYR2 channel complex; (3) structural changes in CSQ2 upon binding of Ca2+ which cause CSQ2 dissociation; (4) the potential role of CSQ2-independent regulation of the RYR2 activity by luminal Ca2+; and (5) the vizualization of CSQ2 dissociation from the RYR2 channel complex on the single channel level. We discuss the potential sources of the conflicting experimental results which may aid detailed understanding of the CSQ2 regulatory role. Although we mainly focus on the cardiac isoform of the proteins, some aspects of more extensive work carried out on the skeletal isoform are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Fabiato A, Fabiato F (1975) Contractions induced by a calcium-triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells. J Physiol 249(3):469–495

    PubMed  CAS  Google Scholar 

  2. Fabiato A, Fabiato F (1978) Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiac and skeletal muscles. J Physiol 276:233–255

    PubMed  CAS  Google Scholar 

  3. Sitsapesan R, Williams AJ (1997) Regulation of current flow through ryanodine receptors by luminal Ca2+. J Membr Biol 159(3):179–185

    Article  PubMed  CAS  Google Scholar 

  4. Gyorke S, Gyorke I, Lukyanenko V, Terentyev D, Viatchenko-Karpinski S, Wiesner TF (2002) Regulation of sarcoplasmic reticulum calcium release by luminal calcium in cardiac muscle. Front Biosci 7:d1454–d1463

    Article  PubMed  CAS  Google Scholar 

  5. Sitsapesan R, Williams AJ (1994) Regulation of the gating of the sheep cardiac sarcoplasmic reticulum Ca(2+)-release channel by luminal Ca2+. J Membr Biol 137(3):215–226

    PubMed  CAS  Google Scholar 

  6. Gyorke I, Gyorke S (1998) Regulation of the cardiac ryanodine receptor channel by luminal Ca2+ involves luminal Ca2+ sensing sites. Biophys J 75(6):2801–2810

    Article  PubMed  CAS  Google Scholar 

  7. Xu L, Meissner G (1998) Regulation of cardiac muscle Ca2+ release channel by sarcoplasmic reticulum lumenal Ca2+. Biophys J 75(5):2302–2312

    Article  PubMed  CAS  Google Scholar 

  8. Gaburjakova J, Gaburjakova M (2006) Comparison of the effects exerted by luminal Ca2+ on the sensitivity of the cardiac ryanodine receptor to caffeine and cytosolic Ca2+. J Membr Biol 212(1):17–28

    Article  PubMed  CAS  Google Scholar 

  9. Qin J, Valle G, Nani A, Nori A, Rizzi N, Priori SG, Volpe P, Fill M (2008) Luminal Ca2+ regulation of single cardiac ryanodine receptors: insights provided by calsequestrin and its mutants. J Gen Physiol 131(4):325–334

    Article  PubMed  CAS  Google Scholar 

  10. Qin J, Valle G, Nani A, Chen H, Ramos-Franco J, Nori A, Volpe P, Fill M (2009) Ryanodine receptor luminal Ca2+ regulation: swapping calsequestrin and channel isoforms. Biophys J 97(7):1961–1970

    Article  PubMed  CAS  Google Scholar 

  11. Tencerova B, Zahradnikova A, Gaburjakova J, Gaburjakova M (2012) Luminal Ca2+ controls activation of the cardiac ryanodine receptor by ATP. J Gen Physiol 140(2):93–108

    Article  PubMed  CAS  Google Scholar 

  12. Laver DR (2007) Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. Biophys J 92(10):3541–3555

    Article  PubMed  CAS  Google Scholar 

  13. Laver DR (2007) Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. Clin Exp Pharmacol Physiol 34(9):889–896

    Article  PubMed  CAS  Google Scholar 

  14. Laver DR (2009) Luminal Ca(2+) activation of cardiac ryanodine receptors by luminal and cytoplasmic domains. Eur Biophys J 39(1):19–26

    Article  PubMed  CAS  Google Scholar 

  15. Ikemoto N, Bhatnagar GM, Nagy B, Gergely J (1972) Interaction of divalent cations with the 55,000-dalton protein component of the sarcoplasmic reticulum. Studies of fluorescence and circular dichroism. J Biol Chem 247(23):7835–7837

    PubMed  CAS  Google Scholar 

  16. MacLennan DH, Wong PT (1971) Isolation of a calcium-sequestering protein from sarcoplasmic reticulum. Proc Natl Acad Sci U S A 68(6):1231–1235

    Article  PubMed  CAS  Google Scholar 

  17. Campbell KP, MacLennan DH, Jorgensen AO, Mintzer MC (1983) Purification and characterization of calsequestrin from canine cardiac sarcoplasmic reticulum and identification of the 53,000 dalton glycoprotein. J Biol Chem 258(2):1197–1204

    PubMed  CAS  Google Scholar 

  18. Scott BT, Simmerman HK, Collins JH, Nadal-Ginard B, Jones LR (1988) Complete amino acid sequence of canine cardiac calsequestrin deduced by cDNA cloning. J Biol Chem 263(18):8958–8964

    PubMed  CAS  Google Scholar 

  19. Guo W, Jorgensen AO, Campbell KP (1996) Triadin, a linker for calsequestrin and the ryanodine receptor. Soc Gen Physiol Ser 51:19–28

    PubMed  CAS  Google Scholar 

  20. Zhang L, Kelley 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(37):23389–23397

    Article  PubMed  CAS  Google Scholar 

  21. Chopra N, Yang T, Asghari P, Moore ED, Huke S, Akin B, Cattolica RA, Perez CF, Hlaing T, Knollmann-Ritschel BE, Jones LR, Pessah IN, Allen PD, Franzini-Armstrong C, Knollmann BC (2009) Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias. Proc Natl Acad Sci U S A 106(18):7636–7641

    Article  PubMed  CAS  Google Scholar 

  22. Beard NA, Laver DR, Dulhunty AF (2004) Calsequestrin and the calcium release channel of skeletal and cardiac muscle. Prog Biophys Mol Biol 85(1):33–69

    Article  PubMed  CAS  Google Scholar 

  23. Herzog A, Szegedi C, Jona I, Herberg FW, Varsanyi M (2000) Surface plasmon resonance studies prove the interaction of skeletal muscle sarcoplasmic reticular Ca(2+) release channel/ryanodine receptor with calsequestrin. FEBS Lett 472(1):73–77

    Article  PubMed  CAS  Google Scholar 

  24. Wei L, Hanna AD, Beard NA, Dulhunty AF (2009) Unique isoform-specific properties of calsequestrin in the heart and skeletal muscle. Cell Calcium 45(5):474–484

    Article  PubMed  CAS  Google Scholar 

  25. Shin DW, Ma J, Kim DH (2000) The asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca(2+) and interacts with triadin. FEBS Lett 486(2):178–182

    Article  PubMed  CAS  Google Scholar 

  26. Kobayashi YM, Alseikhan BA, Jones LR (2000) Localization and characterization of the calsequestrin-binding domain of triadin 1. Evidence for a charged beta-strand in mediating the protein–protein interaction. J Biol Chem 275(23):17639–17646

    Article  PubMed  CAS  Google Scholar 

  27. Gyorke I, Hester N, Jones LR, Gyorke S (2004) The role of calsequestrin, triadin, and junctin in conferring cardiac ryanodine receptor responsiveness to luminal calcium. Biophys J 86(4):2121–2128

    Article  PubMed  Google Scholar 

  28. Ikemoto N, Ronjat M, Meszaros LG, Koshita M (1989) Postulated role of calsequestrin in the regulation of calcium release from sarcoplasmic reticulum. Biochemistry 28(16):6764–6771

    Article  PubMed  CAS  Google Scholar 

  29. Terentyev D, Cala SE, Houle TD, Viatchenko-Karpinski S, Gyorke I, Terentyeva R, Williams SC, Gyorke S (2005) Triadin overexpression stimulates excitation-contraction coupling and increases predisposition to cellular arrhythmia in cardiac myocytes. Circ Res 96(6):651–658

    Article  PubMed  CAS  Google Scholar 

  30. Terentyev D, Viatchenko-Karpinski S, Vedamoorthyrao S, Oduru S, Gyorke I, Williams SC, Gyorke S (2007) Protein protein interactions between triadin and calsequestrin are involved in modulation of sarcoplasmic reticulum calcium release in cardiac myocytes. J Physiol 583(Pt 1):71–80

    Article  PubMed  CAS  Google Scholar 

  31. Wei L, Gallant EM, Dulhunty AF, Beard NA (2009) Junctin and triadin each activate skeletal ryanodine receptors but junctin alone mediates functional interactions with calsequestrin. Int J Biochem Cell Biol 41(11):2214–2224

    Article  PubMed  CAS  Google Scholar 

  32. Terentyev D, Nori A, Santoro M, Viatchenko-Karpinski S, Kubalova Z, Gyorke I, Terentyeva R, Vedamoorthyrao S, Blom NA, Valle G, Napolitano C, Williams SC, Volpe P, Priori SG, Gyorke S (2006) Abnormal interactions of calsequestrin with the ryanodine receptor calcium release channel complex linked to exercise-induced sudden cardiac death. Circ Res 98(9):1151–1158

    Article  PubMed  CAS  Google Scholar 

  33. di Barletta MR, Viatchenko-Karpinski S, Nori A, Memmi M, Terentyev D, Turcato F, Valle G, Rizzi N, Napolitano C, Gyorke S, Volpe P, Priori SG (2006) Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation 114(10):1012–1019

    Article  PubMed  Google Scholar 

  34. Jiang D, Chen W, Wang R, Zhang L, Chen SR (2007) Loss of luminal Ca2+ activation in the cardiac ryanodine receptor is associated with ventricular fibrillation and sudden death. Proc Natl Acad Sci U S A 104(46):18309–18314

    Article  PubMed  CAS  Google Scholar 

  35. Jiang D, Chen W, Xiao J, Wang R, Kong H, Jones PP, Zhang L, Fruen B, Chen SR (2008) Reduced threshold for luminal Ca2+ activation of RyR1 underlies a causal mechanism of porcine malignant hyperthermia. J Biol Chem 283(30):20813–20820

    Article  PubMed  CAS  Google Scholar 

  36. Priori SG, Chen SR (2011) Inherited dysfunction of sarcoplasmic reticulum Ca2+ handling and arrhythmogenesis. Circ Res 108(7):871–883

    Article  PubMed  CAS  Google Scholar 

  37. Beard NA, Sakowska MM, Dulhunty AF, Laver DR (2002) Calsequestrin is an inhibitor of skeletal muscle ryanodine receptor calcium release channels. Biophys J 82(1 Pt 1):310–320

    Article  PubMed  CAS  Google Scholar 

  38. Beard NA, Casarotto MG, Wei L, Varsanyi M, Laver DR, Dulhunty AF (2005) Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+ and phosphorylation. Biophys J 88(5):3444–3454

    Article  PubMed  CAS  Google Scholar 

  39. Dulhunty AF, Wium E, Li L, Hanna AD, Mirza S, Talukder S, Ghazali NA, Beard NA (2012) Proteins within the intracellular calcium store determine cardiac RyR channel activity and cardiac output. Clin Exp Pharmacol Physiol 39(5):477–484

    Article  PubMed  CAS  Google Scholar 

  40. Murphy RM, Mollica JP, Beard NA, Knollmann BC, Lamb GD (2011) Quantification of calsequestrin 2 (CSQ2) in sheep cardiac muscle and Ca2+ -binding protein changes in CSQ2 knockout mice. Am J Physiol Heart Circ Physiol 300(2):H595–H604

    Article  PubMed  CAS  Google Scholar 

  41. Viatchenko-Karpinski S, Terentyev D, Gyorke I, Terentyeva R, Volpe P, Priori SG, Napolitano C, Nori A, Williams SC, Gyorke S (2004) Abnormal calcium signaling and sudden cardiac death associated with mutation of calsequestrin. Circ Res 94(4):471–477

    Article  PubMed  CAS  Google Scholar 

  42. Wei L, Varsanyi M, Dulhunty AF, Beard NA (2006) The conformation of calsequestrin determines its ability to regulate skeletal ryanodine receptors. Biophys J 91(4):1288–1301

    Article  PubMed  CAS  Google Scholar 

  43. Park H, Park IY, Kim E, Youn B, Fields K, Dunker AK, Kang C (2004) Comparing skeletal and cardiac calsequestrin structures and their calcium binding: a proposed mechanism for coupled calcium binding and protein polymerization. J Biol Chem 279(17):18026–18033

    Article  PubMed  CAS  Google Scholar 

  44. Mitchell RD, Simmerman HK, Jones LR (1988) Ca2+ binding effects on protein conformation and protein interactions of canine cardiac calsequestrin. J Biol Chem 263(3):1376–1381

    PubMed  CAS  Google Scholar 

  45. Chopra N, Knollmann BC (2009) Cardiac calsequestrin: the new kid on the block in arrhythmias. J Cardiovasc Electrophysiol 20(10):1179–1185

    Article  PubMed  Google Scholar 

  46. MacLennan DH (1813) Zvaritch E (2011) Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum. Biochim Biophys Acta 5:948–964

    Google Scholar 

  47. Faggioni M, Knollmann BC (2012) Calsequestrin 2 and arrhythmias. Am J Physiol Heart Circ Physiol 302(6):H1250–H1260

    Article  PubMed  CAS  Google Scholar 

  48. Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C (2007) Characterization of human cardiac calsequestrin and its deleterious mutants. J Mol Biol 373(4):1047–1057

    Article  PubMed  CAS  Google Scholar 

  49. Bal NC, Sharon A, Gupta SC, Jena N, Shaikh S, Gyorke S, Periasamy M (2010) The catecholaminergic polymorphic ventricular tachycardia mutation R33Q disrupts the N-terminal structural motif that regulates reversible calsequestrin polymerization. J Biol Chem 285(22):17188–17196

    Article  PubMed  CAS  Google Scholar 

  50. Sanchez EJ, Lewis KM, Danna BR, Kang C (2012) High-capacity Ca2+-binding of human skeletal calsequestrin. J Biol Chem 287:11592–11601

    Article  PubMed  CAS  Google Scholar 

  51. Slupsky JR, Ohnishi M, Carpenter MR, Reithmeier RA (1987) Characterization of cardiac calsequestrin. Biochemistry 26(20):6539–6544

    Article  PubMed  CAS  Google Scholar 

  52. Wang S, Trumble WR, Liao H, Wesson CR, Dunker AK, Kang CH (1998) Crystal structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum. Nat Struct Biol 5(6):476–483

    Article  PubMed  CAS  Google Scholar 

  53. Park H, Wu S, Dunker AK, Kang C (2003) Polymerization of calsequestrin. Implications for Ca2+ regulation. J Biol Chem 278(18):16176–16182

    Article  PubMed  CAS  Google Scholar 

  54. Valle G, Galla D, Nori A, Priori SG, Gyorke S, de Filippis V, Volpe P (2008) Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin. Biochem J 413(2):291–303

    Article  PubMed  CAS  Google Scholar 

  55. Kalyanasundaram A, Bal NC, Franzini-Armstrong C, Knollmann BC, Periasamy M (2010) The calsequestrin mutation CASQ2D307H does not affect protein stability and targeting to the junctional sarcoplasmic reticulum but compromises its dynamic regulation of calcium buffering. J Biol Chem 285(5):3076–3083

    Article  PubMed  CAS  Google Scholar 

  56. Bal NC, Jena N, Sopariwala D, Balaraju T, Shaikh S, Bal C, Sharon A, Gyorke S, Periasamy M (2011) Probing cationic selectivity of cardiac calsequestrin and its CPVT mutants. Biochem J 435(2):391–399

    Article  PubMed  CAS  Google Scholar 

  57. Mishra A, Suman SK, Srivastava SS, Sankaranarayanan R, Sharma Y (2012) Decoding the molecular design principles underlying Ca(2+) binding to betagamma-crystallin motifs. J Mol Biol 415(1):75–91

    Article  PubMed  CAS  Google Scholar 

  58. Launikonis BS, Zhou J, Royer L, Shannon TR, Brum G, Rios E (2006) Depletion “skraps” and dynamic buffering inside the cellular calcium store. Proc Natl Acad Sci U S A 103(8):2982–2987

    Article  PubMed  CAS  Google Scholar 

  59. Chopra N, Kannankeril PJ, Yang T, Hlaing T, Holinstat I, Ettensohn K, Pfeifer K, Akin B, Jones LR, Franzini-Armstrong C, Knollmann BC (2007) Modest reductions of cardiac calsequestrin increase sarcoplasmic reticulum Ca2+ leak independent of luminal Ca2+ and trigger ventricular arrhythmias in mice. Circ Res 101(6):617–626

    Article  PubMed  CAS  Google Scholar 

  60. Stevens SC, Terentyev D, Kalyanasundaram A, Periasamy M, Gyorke S (2009) Intra-sarcoplasmic reticulum Ca2+ oscillations are driven by dynamic regulation of ryanodine receptor function by luminal Ca2+ in cardiomyocytes. J Physiol 587(Pt 20):4863–4872

    Article  PubMed  CAS  Google Scholar 

  61. Lee KW, Maeng JS, Choi JY, Lee YR, Hwang CY, Park SS, Park HK, Chung BH, Lee SG, Kim YS, Jeon H, Eom SH, Kang C, Kim do H, Kwon KS (2012) Role of Junctin protein interactions in cellular dynamics of calsequestrin polymer upon calcium perturbation. J Biol Chem 287(3):1679–1687

    Article  PubMed  CAS  Google Scholar 

  62. Franzini-Armstrong C, Protasi F, Tijskens P (2005) The assembly of calcium release units in cardiac muscle. Ann N Y Acad Sci 1047:76–85

    Article  PubMed  CAS  Google Scholar 

  63. Jones LR, Suzuki YJ, Wang W, Kobayashi YM, Ramesh V, Franzini-Armstrong C, Cleemann L, Morad M (1998) Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin. J Clin Invest 101(7):1385–1393

    Article  PubMed  CAS  Google Scholar 

  64. Zhang L, Franzini-Armstrong C, Ramesh V, Jones LR (2001) Structural alterations in cardiac calcium release units resulting from overexpression of junctin. J Mol Cell Cardiol 33(2):233–247

    Article  PubMed  CAS  Google Scholar 

  65. Terentyev D, Viatchenko-Karpinski S, Valdivia HH, Escobar AL, Gyorke S (2002) Luminal Ca2+ controls termination and refractory behavior of Ca2+ -induced Ca2+ release in cardiac myocytes. Circ Res 91(5):414–420

    Article  PubMed  CAS  Google Scholar 

  66. Baksh S, Spamer C, Oikawa K, McCubbin WD, Heilmann C, Kay CM, Michalak M (1995) Zn2+ binding to cardiac calsequestrin. Biochem Biophys Res Commun 209(1):310–315

    Article  PubMed  CAS  Google Scholar 

  67. Ikemoto N, Nagy B, Bhatnagar GM, Gergely J (1974) Studies on a metal-binding protein of the sarcoplasmic reticulum. J Biol Chem 249(8):2357–2365

    PubMed  CAS  Google Scholar 

  68. Xie H, Chen KY, Zhu PH (2004) Effect of Zn2+ ions on ryanodine binding to sarcoplasmic reticulum of striated muscles in the presence of pyrithione. Acta Pharmacol Sin 25(12):1647–1651

    PubMed  CAS  Google Scholar 

  69. Palmer BM, Vogt S, Chen Z, Lachapelle RR, Lewinter MM (2006) Intracellular distributions of essential elements in cardiomyocytes. J Struct Biol 155(1):12–21

    Article  PubMed  CAS  Google Scholar 

  70. Laver DR, Honen BN (2008) Luminal Mg2+, a key factor controlling RYR2-mediated Ca2+ release: cytoplasmic and luminal regulation modeled in a tetrameric channel. J Gen Physiol 132(4):429–446

    Article  PubMed  CAS  Google Scholar 

  71. Kirchhefer U, Neumann J, Bers DM, Buchwalow IB, Fabritz L, Hanske G, Justus I, Riemann B, Schmitz W, Jones LR (2003) Impaired relaxation in transgenic mice overexpressing junctin. Cardiovasc Res 59(2):369–379

    Article  PubMed  CAS  Google Scholar 

  72. Tijskens P, Jones LR, Franzini-Armstrong C (2003) Junctin and calsequestrin overexpression in cardiac muscle: the role of junctin and the synthetic and delivery pathways for the two proteins. J Mol Cell Cardiol 35(8):961–974

    Article  PubMed  CAS  Google Scholar 

  73. Kirchhefer U, Hanske G, Jones LR, Justus I, Kaestner L, Lipp P, Schmitz W, Neumann J (2006) Overexpression of junctin causes adaptive changes in cardiac myocyte Ca(2+) signaling. Cell Calcium 39(2):131–142

    Article  PubMed  CAS  Google Scholar 

  74. Yuan Q, Fan GC, Dong M, Altschafl B, Diwan A, Ren X, Hahn HH, Zhao W, Waggoner JR, Jones LR, Jones WK, Bers DM, Dorn GW 2nd, Wang HS, Valdivia HH, Chu G, Kranias EG (2007) Sarcoplasmic reticulum calcium overloading in junctin deficiency enhances cardiac contractility but increases ventricular automaticity. Circulation 115(3):300–309

    Article  PubMed  CAS  Google Scholar 

  75. Altschafl BA, Arvanitis DA, Fuentes O, Yuan Q, Kranias EG, Valdivia HH (2011) Dual role of junctin in the regulation of ryanodine receptors and calcium release in cardiac ventricular myocytes. J Physiol 589(Pt 24):6063–6080

    PubMed  CAS  Google Scholar 

  76. Postma AV, Denjoy I, Hoorntje TM, Lupoglazoff JM, Da Costa A, Sebillon P, Mannens MM, Wilde AA, Guicheney P (2002) Absence of calsequestrin 2 causes severe forms of catecholaminergic polymorphic ventricular tachycardia. Circ Res 91(8):e21–e26

    Article  PubMed  CAS  Google Scholar 

  77. Knollmann BC, Chopra N, Hlaing T, Akin B, Yang T, Ettensohn K, Knollmann BE, Horton KD, Weissman NJ, Holinstat I, Zhang W, Roden DM, Jones LR, Franzini-Armstrong C, Pfeifer K (2006) Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia. J Clin Invest 116(9):2510–2520

    PubMed  CAS  Google Scholar 

  78. Song L, Alcalai R, Arad M, Wolf CM, Toka O, Conner DA, Berul CI, Eldar M, Seidman CE, Seidman JG (2007) Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and ryanodine receptors, causing catecholaminergic polymorphic ventricular tachycardia. J Clin Invest 117(7):1814–1823

    Article  PubMed  CAS  Google Scholar 

  79. Jiang D, Wang R, Xiao B, Kong H, Hunt DJ, Choi P, Zhang L, Chen SR (2005) Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ Res 97(11):1173–1181

    Article  PubMed  CAS  Google Scholar 

  80. Jones PP, Jiang D, Bolstad J, Hunt DJ, Zhang L, Demaurex N, Chen SR (2008) Endoplasmic reticulum Ca2+ measurements reveal that the cardiac ryanodine receptor mutations linked to cardiac arrhythmia and sudden death alter the threshold for store-overload-induced Ca2+ release. Biochem J 412(1):171–178

    Article  PubMed  CAS  Google Scholar 

  81. Szegedi C, Sarkozi S, Herzog A, Jona I, Varsanyi M (1999) Calsequestrin: more than ‘only’ a luminal Ca2+ buffer inside the sarcoplasmic reticulum. Biochem J 337(Pt 1):19–22

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Slovak Grant Agency (VEGA) (Grants 2/0102/12 to J.G. and 2/0033/11 to M.G.), and National Institutes of Health (Grant R01 HL64014 to M. P). N.C.B. was supported by postdoctoral fellowships (10POST3360007) from the American Heart Association.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34, Bratislava, Slovak Republic

    Marta Gaburjakova & Jana Gaburjakova

  2. Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA

    Naresh C. Bal & Muthu Periasamy

Authors
  1. Marta Gaburjakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naresh C. Bal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jana Gaburjakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muthu Periasamy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marta Gaburjakova.

Additional information

M. Gaburjakova and N. C. Bal contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gaburjakova, M., Bal, N.C., Gaburjakova, J. et al. Functional interaction between calsequestrin and ryanodine receptor in the heart. Cell. Mol. Life Sci. 70, 2935–2945 (2013). https://doi.org/10.1007/s00018-012-1199-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-012-1199-7

Keywords

Search

Navigation