Hyperphosphorylation of RyRs underlies triggered activity in transgenic rabbit model of LQT2 syndrome

Circulation Research

Volumn 115, Issue 11, 2014, Pages 919-928

  Terentyev, Dmitry ^a   Rees, Colin M ^b   Li, Weiyan ^a   Cooper, Leroy L ^a   Jindal, Hitesh K ^a   Peng, Xuwen ^c   Lu, Yichun ^a   Terentyeva, Radmila ^a   Odening, Katja E ^d   Daley, Jean ^a   Bist, Kamana ^a   Choi, Bum Rak ^a   Karma, Alain ^b   Koren, Gideon ^a  

^a BROWN UNIVERSITY   (United States)

^b NORTHEASTERN UNIVERSITY   (United States)

^c PENN STATE COLLEGE OF MEDICINE   (United States)

^d UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Arrhythmias; Calcium release; Cardiac; Long QT syndrome; Protein phosphatase; Ryanodine receptor

Indexed keywords

CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CALCIUM ION; ISOPRENALINE; PHOSPHOPROTEIN PHOSPHATASE 1; PHOSPHOPROTEIN PHOSPHATASE 2; RYANODINE RECEPTOR; SODIUM CALCIUM EXCHANGE PROTEIN; CALCIUM CHANNEL L TYPE; ERG1 POTASSIUM CHANNEL; POTASSIUM CHANNEL HERG;

ACTION POTENTIAL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CALCIUM TRANSPORT; CHROMATIN IMMUNOPRECIPITATION; COMPUTER SIMULATION; CONTROLLED STUDY; HEART DEPOLARIZATION; HEART MUSCLE CELL; LONG QT SYNDROME 2; NONHUMAN; PRIORITY JOURNAL; PROTEIN HYPERPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; SARCOPLASMIC RETICULUM; WESTERN BLOTTING; ANIMAL; CALCIUM SIGNALING; CELL CULTURE; CYTOLOGY; GENETICS; HEART VENTRICLE; HUMAN; LONG QT SYNDROME; METABOLISM; PATHOPHYSIOLOGY; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN PROCESSING; RABBIT; TRANSGENIC ANIMAL;

ACTION POTENTIALS; ANIMALS; ANIMALS, GENETICALLY MODIFIED; CALCIUM CHANNELS, L-TYPE; CALCIUM SIGNALING; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CELLS, CULTURED; ETHER-A-GO-GO POTASSIUM CHANNELS; HEART VENTRICLES; HUMANS; LONG QT SYNDROME; MYOCYTES, CARDIAC; PHOSPHORYLATION; PROTEIN PHOSPHATASE 1; PROTEIN PHOSPHATASE 2; PROTEIN PROCESSING, POST-TRANSLATIONAL; RABBITS; RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL; SODIUM-CALCIUM EXCHANGER;

EID: 84922391402     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.115.305146     Document Type: Article

References (41)

1. Cerrone M, Priori SG. Genetics of sudden death: focus on inherited channelopathies. Eur Heart J. 2011;32:2109-2118.
2. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D. Risk stratification in the long-QT syndrome. N Engl J Med. 2003;348:1866-1874.
3. Antzelevitch C. Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes. Europace. 2007;9:iv4-iv15.
4. Weiss JN, Garfinkel A, Karagueuzian HS, Chen PS, Qu Z. Early after depolarizations and cardiac arrhythmias. Heart Rhythm. 2010;7:1891-1899.
5. Brunner M, Peng X, Liu GX, et al. Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. J Clin Invest. 2008;118:2246-2259.
6. Ziv O, Morales E, Song YK, Peng X, Odening KE, Buxton AE, Karma A, Koren G, Choi BR. Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome. J Physiol. 2009;587:4661-4680.
7. Liu GX, Choi BR, Ziv O, Li W, de Lange E, Qu Z, Koren G. Differential conditions for early after-depolarizations and triggered activity in cardiomyocytes derived from transgenic LQT1 and LQT2 rabbits. J Physiol. 2012;590:1171-1180.
8. ter Bekke RM, Volders PG. Arrhythmogenic mechano-electric heterogeneity in the long-QT syndrome. Prog Biophys Mol Biol. 2012;110:347-358.
9. Odening KE, Choi BR, Liu GX, Hartmann K, Ziv O, Chaves L, Schofield L, Centracchio J, Zehender M, Peng X, Brunner M, Koren G. Estradiol promotes sudden cardiac death in transgenic long QT type 2 rabbits while progesterone is protective. Heart Rhythm. 2012;9:823-832.
10. Tran DX, Sato D, Yochelis A, Weiss JN, Garfinkel A, Qu Z. Bifurcation and chaos in a model of cardiac early afterdepolarizations. Phys Rev Lett. 2009;102:258103.
11. Qu Z, Xie LH, Olcese R, Karagueuzian HS, Chen PS, Garfinkel A, Weiss JN. Early afterdepolarizations in cardiac myocytes: beyond reduced repolarization reserve. Cardiovasc Res. 2013;99:6-15.
12. Parikh A, Mantravadi R, Kozhevnikov D, Roche MA, Ye Y, Owen LJ, Puglisi JL, Abramson JJ, Salama G. Ranolazine stabilizes cardiac ryanodine receptors: a novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2. Heart Rhythm. 2012;9:953-960.
13. Xie Y, Grandi E, Puglisi JL, Sato D, Bers DM. β-adrenergic stimulation activates early afterdepolarizations transiently via kinetic mismatch of PKA targets. J Mol Cell Cardiol. 2013;58:153-161.
14. Belevych AE, Terentyev D, Terentyeva R, Ho HT, Gyorke I, Bonilla IM, Carnes CA, Billman GE, Györke S. Shortened Ca2+ signaling refractoriness underlies cellular arrhythmogenesis in a postinfarction model of sudden cardiac death. Circ Res. 2012;110:569-577.
15. Belevych AE, Terentyev D, Terentyeva R, Nishijima Y, Sridhar A, Hamlin RL, Carnes CA, Györke S. The relationship between arrhythmogenesis and impaired contractility in heart failure: role of altered ryanodine receptor function. Cardiovasc Res. 2011;90:493-502.
16. Belevych AE, Sansom SE, Terentyeva R, Ho HT, Nishijima Y, Martin MM, Jindal HK, Rochira JA, Kunitomo Y, Abdellatif M, Carnes CA, Elton TS, Györke S, Terentyev D. MicroRNA-1 and -133 increase arrhythmogenesis in heart failure by dissociating phosphatase activity from RyR2 complex. PLoS One. 2011;6:e28324.
17. Restrepo JG, Weiss JN, Karma A. Calsequestrin-mediated mechanism for cellular calcium transient alternans. Biophys J. 2008;95:3767-3789.
18. Restrepo JG, Karma A. Spatiotemporal intracellular calcium dynamics during cardiac alternans. Chaos. 2009;19:037115.
19. Zima AV, Bovo E, Bers DM, Blatter LA. Ca2+ spark-dependent and -independent sarcoplasmic reticulum Ca2+ leak in normal and failing rabbit ventricular myocytes. J Physiol. 2010;588:4743-4757.
20. Zima AV, Bovo E, Mazurek SR, Rochira JA, Li W, Terentyev D. Ca handling during excitation-contraction coupling in heart failure. Pflugers Arch. 2014;466:1129-1137.
21. Currie S, Smith GL. Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure. Cardiovasc Res. 1999;41:135-146.
22. Ai X, Curran JW, Shannon TR, Bers DM, Pogwizd SM. Ca2+/calmodulindependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. Circ Res. 2005;97:1314-1322.
23. Cooper LL, Li W, Lu Y, Centracchio J, Terentyeva R, Koren G, Terentyev D. Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts. J Physiol. 2013;591:5895-5911.
24. McCauley MD, Wehrens XH. Ryanodine receptor phosphorylation, calcium/calmodulin-dependent protein kinase II, and life-threatening ventricular arrhythmias. Trends Cardiovasc Med. 2011;21:48-51.
25. Bers DM. Macromolecular complexes regulating cardiac ryanodine receptor function. J Mol Cell Cardiol. 2004;37:417-429.
26. Kushnir A, Shan J, Betzenhauser MJ, Reiken S, Marks AR. Role of CaMKIIdelta phosphorylation of the cardiac ryanodine receptor in the force frequency relationship and heart failure. Proc Natl Acad Sci USA. 2010;107:10274-10279.
27. Reiken S, Gaburjakova M, Guatimosim S, Gomez AM, D'Armiento J, Burkhoff D, Wang J, Vassort G, Lederer WJ, Marks AR. Protein kinase A phosphorylation of the cardiac calcium release channel (ryanodine receptor) in normal and failing hearts. Role of phosphatases and response to isoproterenol. J Biol Chem. 2003;278:444-453.
28. Di Pasquale E, Lodola F, Miragoli M, Denegri M, Avelino-Cruz JE, Buonocore M, Nakahama H, Portararo P, Bloise R, Napolitano C, Condorelli G, Priori SG. CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia. Cell Death Dis. 2013;4:e843.
29. DeGrande S, Nixon D, Koval O, Curran JW, Wright P, Wang Q, Kashef F, Chiang D, Li N, Wehrens XH, Anderson ME, Hund TJ, Mohler PJ. CaMKII inhibition rescues proarrhythmic phenotypes in the model of human ankyrin-B syndrome. Heart Rhythm. 2012;9:2034-2041.
30. Loaiza R, Benkusky NA, Powers PP, Hacker T, Noujaim S, Ackerman MJ, Jalife J, Valdivia HH. Heterogeneity of ryanodine receptor dysfunction in a mouse model of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2013;112:298-308.
31. Odening KE, Jung BA, Lang CN, Cabrera Lozoya R, Ziupa D, Menza M, Relan J, Franke G, Perez Feliz S, Koren G, Zehender M, Bode C, Brunner M, Sermesant M, Föll D. Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits. Heart Rhythm. 2013;10:1533-1541.
32. Newgard CB, Brady MJ, O'Doherty RM, Saltiel AR. Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1. Diabetes. 2000;49:1967-1977.
33. Jindal HK, Merchant E, Balschi JA, Zhangand Y, Koren G. Proteomic analyses of transgenic LQT1 and LQT2 rabbit hearts elucidate an increase in expression and activity of energy producing enzymes. J Proteomics. 2012;75:5254-5265.
34. DeGrande ST, Little SC, Nixon DJ, Wright P, Snyder J, Dun W, Murphy N, Kilic A, Higgins R, Binkley PF, Boyden PA, Carnes CA, Anderson ME, Hund TJ, Mohler PJ. Molecular mechanisms underlying cardiac protein phosphatase 2A regulation in heart. J Biol Chem. 2013;288:1032-1046.
35. Ogris E, Gibson DM, Pallas DC. Protein phosphatase 2A subunit assembly: the catalytic subunit carboxy terminus is important for binding cellular B subunit but not polyomavirus middle tumor antigen. Oncogene. 1997;15:911-917.
36. Qi X, Yeh YH, Chartier D, Xiao L, Tsuji Y, Brundel BJ, Kodama I, Nattel S. The calcium/calmodulin/kinase system and arrhythmogenic afterdepolarizations in bradycardia-related acquired long-QT syndrome. Circ Arrhythm Electrophysiol. 2009;2:295-304.
37. Shannon TR, Wang F, Puglisi J, Weber C, Bers DM. A mathematical treatment of integrated Ca dynamics within the ventricular myocyte. Biophys J. 2004;87:3351-3371.
38. Mahajan A, Shiferaw Y, Sato D, Baher A, Olcese R, Xie LH, Yang MJ, Chen PS, Restrepo JG, Karma A, Garfinkel A, Qu Z, Weiss JN. A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates. Biophys J. 2008;94:392-410.
39. Zhao Z, Wen H, Fefelova N, Allen C, Baba A, Matsuda T, Xie LH. Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents? Am J Physiol Heart Circ Physiol. 2012;302:H1636-H1644.
40. Venetucci LA, Trafford AW, O'Neill SC, Eisner DA. The sarcoplasmic reticulum and arrhythmogenic calcium release. Cardiovasc Res. 2008;77:285-292.
41. Radwanski PB, Belevych AE, Brunello L, Carnes CA, Györke S. Storedependent deactivation: cooling the chain-reaction of myocardial calcium signaling. J Mol Cell Cardiol. 2013;58:77-83.