The Ca-calmodulin dependent kinase II: A promising target for future antiarrhythmic therapies?

Journal of Molecular and Cellular Cardiology

Volumn 58, Issue 1, 2013, Pages 182-187

  Fischer, Thomas H ^a   Neef, Stefan ^a   Maier, Lars S ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

Afterdepolarizations; Arrhythmias; Calcium cycling; CaMKII; Ion channels; Phosphorylation

Indexed keywords

ANTIARRHYTHMIC AGENT; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CALCIUM CHANNEL L TYPE; PHOSPHOLAMBAN; POTASSIUM CHANNEL; RYANODINE RECEPTOR 2; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SERCA2A PROTEIN; SODIUM CHANNEL; UNCLASSIFIED DRUG;

CALCIUM CYCLING; CALCIUM SIGNALING; CALCIUM TRANSPORT; CHANNEL GATING; CYTOSOL; DISEASE ASSOCIATION; DRUG RESEARCH; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART DEPOLARIZATION; HEART FAILURE; HEART MUSCLE POTENTIAL; LONG QT SYNDROME; MOLECULARLY TARGETED THERAPY; POTASSIUM TRANSPORT; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; REVIEW; SARCOLEMMA; SARCOPLASMIC RETICULUM; SINUS RHYTHM; SODIUM TRANSPORT;

ANTI-ARRHYTHMIA AGENTS; ARRHYTHMIAS, CARDIAC; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CYTOSOL; HUMANS; MOLECULAR TARGETED THERAPY; SARCOLEMMA;

EID: 84876326824     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2012.11.003     Document Type: Review

References (65)

1. Camm A.J., Kirchhof P., Lip G.Y., Schotten U., Savelieva I., Ernst S., et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace 2010, 12:1360-1420.
2. Packer M. Sudden unexpected death in patients with congestive heart failure: a second frontier. Circulation 1985, 72:681-685.
3. Davies M., Hobbs F., Davis R., Kenkre J., Roalfe A.K., Hare R., et al. Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study. Lancet 2001, 358:439-444.
4. Mosterd A., Cost B., Hoes A.W., de Bruijne M.C., Deckers J.W., Hofman A., et al. The prognosis of heart failure in the general population: The Rotterdam Study. Eur Heart J 2001, 22:1318-1327.
5. MacIntyre K., Capewell S., Stewart S., Chalmers J.W., Boyd J., Finlayson A., et al. Evidence of improving prognosis in heart failure: trends in case fatality in 66,547 patients hospitalized between 1986 and 1995. Circulation 2000, 102:1126-1131.
6. Cowie M.R., Wood D.A., Coats A.J., Thompson S.G., Suresh V., Poole-Wilson P.A., et al. Survival of patients with a new diagnosis of heart failure: a population based study. Heart 2000, 83:505-510.
7. Krell M.J., Kline E.M., Bates E.R., Hodgson J.M., Dilworth L.R., Laufer N., et al. Intermittent, ambulatory dobutamine infusions in patients with severe congestive heart failure. Am Heart J 1986, 112:787-791.
8. Greenberg H.M., Dwyer E.M., Hochman J.S., Steinberg J.S., Echt D.S., Peters R.W. Interaction of ischaemia and encainide/flecainide treatment: a proposed mechanism for the increased mortality in CAST I. Br Heart J 1995, 74:631-635.
9. Rokita A.G., Anderson M.E. New therapeutic targets in cardiology: arrhythmias and Ca2+/calmodulin-dependent kinase II (CaMKII). Circulation 2012, 126:2125-2139.
10. Witcher D.R., Kovacs R.J., Schulman H., Cefali D.C., Jones L.R. Unique phosphorylation site on the cardiac ryanodine receptor regulates calcium channel activity. J Biol Chem 1991, 266:11144-11152.
11. Wehrens X.H., Lehnart S.E., Reiken S.R., Marks A.R. Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor. Circ Res 2004, 94:e61-e70.
12. Mattiazzi A., Kranias E.G. CaMKII regulation of phospholamban and SR Ca2+ load. Heart Rhythm 2011, 8:784-787.
13. Dzhura I., Wu Y., Colbran R.J., Balser J.R., Anderson M.E. Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol 2000, 2:173-177.
14. Wagner S., Dybkova N., Rasenack E.C., Jacobshagen C., Fabritz L., Kirchhof P., et al. Ca2+/calmodulin-dependent protein kinase II regulates cardiac Na+ channels. J Clin Invest 2006, 116:3127-3138.
15. Kushnir A., Shan J., Betzenhauser M.J., Reiken S., Marks A.R. Role of CaMKIIdelta phosphorylation of the cardiac ryanodine receptor in the force frequency relationship and heart failure. Proc Natl Acad Sci U S A 2010, 107:10274-10279.
16. Wu Y., Gao Z., Chen B., Koval O.M., Singh M.V., Guan X., et al. Calmodulin kinase II is required for fight or flight sinoatrial node physiology. Proc Natl Acad Sci U S A 2009, 106:5972-5977.
17. DeSantiago J., Maier L.S., Bers D.M. Phospholamban is required for CaMKII-dependent recovery of Ca transients and SR Ca reuptake during acidosis in cardiac myocytes. J Mol Cell Cardiol 2004, 36:67-74.
18. Sag C.M., Dybkova N., Neef S., Maier L.S. Effects on recovery during acidosis in cardiac myocytes overexpressing CaMKII. J Mol Cell Cardiol 2007, 43:696-709.
19. Maier L.S., Zhang T., Chen L., DeSantiago J., Brown J.H., Bers D.M. Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release. Circ Res 2003, 92:904-911.
20. Sag C.M., Wadsack D.P., Khabbazzadeh S., Abesser M., Grefe C., Neumann K., et al. Calcium/calmodulin-dependent protein kinase II contributes to cardiac arrhythmogenesis in heart failure. Circ Heart Fail 2009, 2:664-675.
21. Meyer T., Hanson P.I., Stryer L., Schulman H. Calmodulin trapping by calcium-calmodulin-dependent protein kinase. Science 1992, 256:1199-1202.
22. He B.J., Joiner M.L., Singh M.V., Luczak E.D., Swaminathan P.D., Koval O.M., et al. Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nat Med 2011, 17:1610-1618.
23. Erickson J.R., Joiner M.L., Guan X., Kutschke W., Yang J., Oddis C.V., et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 2008, 133:462-474.
24. Hasenfuss G. Alterations of calcium-regulatory proteins in heart failure. Cardiovasc Res 1998, 37:279-289.
25. Neef S., Dybkova N., Sossalla S., Ort K.R., Fluschnik N., Neumann K., et al. CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation. Circ Res 2010, 106:1134-1144.
26. Voigt N., Li N., Wang Q., Wang W., Trafford A.W., Abu-Taha I., et al. Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation 2012, 125:2059-2070.
27. Zhang T., Maier L.S., Dalton N.D., Miyamoto S., Ross J., Bers D.M., et al. The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circ Res 2003, 92:912-919.
28. Kohlhaas M., Zhang T., Seidler T., Zibrova D., Dybkova N., Steen A., et al. Increased sarcoplasmic reticulum calcium leak but unaltered contractility by acute CaMKII overexpression in isolated rabbit cardiac myocytes. Circ Res 2006, 98:235-244.
29. Sossalla S., Fluschnik N., Schotola H., Ort K.R., Neef S., Schulte T., et al. Inhibition of elevated Ca2+/calmodulin-dependent protein kinase II improves contractility in human failing myocardium. Circ Res 2010, 107:1150-1161.
30. Toischer K., Rokita A.G., Unsold B., Zhu W., Kararigas G., Sossalla S., et al. Differential cardiac remodeling in preload versus afterload. Circulation 2010, 122:993-1003.
31. Endo M. Calcium release from the sarcoplasmic reticulum. Physiol Rev 1977, 57:71-108.
32. Bers D.M. Cardiac excitation-contraction coupling. Nature 2002, 415:198-205.
33. Song Y., Shryock J.C., Belardinelli L. An increase of late sodium current induces delayed afterdepolarizations and sustained triggered activity in atrial myocytes. Am J Physiol Heart Circ Physiol 2008, 294:H2031-H2039.
34. Pieske B., Maier L.S., Bers D.M., Hasenfuss G. Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium. Circ Res 1999, 85:38-46.
35. Hasenfuss G., Schillinger W., Lehnart S.E., Preuss M., Pieske B., Maier L.S., et al. Relationship between Na+-Ca2+-exchanger protein levels and diastolic function of failing human myocardium. Circulation 1999, 99:641-648.
36. Dybkova N., Sedej S., Napolitano C., Neef S., Rokita A.G., Hunlich M., et al. Overexpression of CaMKIIdeltac in RyR2R4496C+/- knock-in mice leads to altered intracellular Ca2+ handling and increased mortality. J Am Coll Cardiol 2011, 57:469-479.
37. Curran J., Brown K.H., Santiago D.J., Pogwizd S., Bers D.M., Shannon T.R. Spontaneous Ca waves in ventricular myocytes from failing hearts depend on Ca(2+)-calmodulin-dependent protein kinase II. J Mol Cell Cardiol 2010, 49:25-32.
38. Gonano L.A., Sepulveda M., Rico Y., Kaetzel M., Valverde C.A., Dedman J., et al. Calcium-calmodulin kinase II mediates digitalis-induced arrhythmias. Circ Arrhythm Electrophysiol 2011, 4:947-957.
39. Chelu M.G., Sarma S., Sood S., Wang S., van Oort R.J., Skapura D.G., et al. Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice. J Clin Invest 2009, 119:1940-1951.
40. Li N., Wang T., Wang W., Cutler M.J., Wang Q., Voigt N., et al. Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circ Res 2012, 110:465-470.
41. Catterall W.A. Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 2000, 16:521-555.
42. Song L.S., Sobie E.A., McCulle S., Lederer W.J., Balke C.W., Cheng H. Orphaned ryanodine receptors in the failing heart. Proc Natl Acad Sci U S A 2006, 103:4305-4310.
43. Koval O.M., Guan X., Wu Y., Joiner M.L., Gao Z., Chen B., et al. CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations. Proc Natl Acad Sci U S A 2010, 107:4996-5000.
44. Wu Y., MacMillan L.B., McNeill R.B., Colbran R.J., Anderson M.E. CaM kinase augments cardiac L-type Ca2+ current: a cellular mechanism for long Q-T arrhythmias. Am J Physiol 1999, 276:H2168-H2178.
45. Anderson M.E., Braun A.P., Wu Y., Lu T., Schulman H., Sung R.J. KN-93, an inhibitor of multifunctional Ca++/calmodulin-dependent protein kinase, decreases early afterdepolarizations in rabbit heart. J Pharmacol Exp Ther 1998, 287:996-1006.
46. Wit A.L., Rosen M.R. Pathophysiologic mechanisms of cardiac arrhythmias. Am Heart J 1983, 106:798-811.
47. Mazur A., Roden D.M., Anderson M.E. Systemic administration of calmodulin antagonist W-7 or protein kinase A inhibitor H-8 prevents torsade de pointes in rabbits. Circulation 1999, 100:2437-2442.
48. Hullin R., Matthes J., von Vietinghoff S., Bodi I., Rubio M., D'Souza K., et al. Increased expression of the auxiliary beta(2)-subunit of ventricular L-type Ca(2)+ channels leads to single-channel activity characteristic of heart failure. PLoS One 2007, 2:e292.
49. Coraboeuf E., Deroubaix E., Coulombe A. Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am J Physiol 1979, 236:H561-H567.
50. Undrovinas A.I., Fleidervish I.A., Makielski J.C. Inward sodium current at resting potentials in single cardiac myocytes induced by the ischemic metabolite lysophosphatidylcholine. Circ Res 1992, 71:1231-1241.
51. Undrovinas A.I., Maltsev V.A., Sabbah H.N. Repolarization abnormalities in cardiomyocytes of dogs with chronic heart failure: role of sustained inward current. Cell Mol Life Sci 1999, 55:494-505.
52. Ward C.A., Giles W.R. Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes. J Physiol 1997, 500(Pt 3):631-642.
53. Tan H.L., Kupershmidt S., Zhang R., Stepanovic S., Roden D.M., Wilde A.A., et al. A calcium sensor in the sodium channel modulates cardiac excitability. Nature 2002, 415:442-447.
54. Wagner S., Ruff H.M., Weber S.L., Bellmann S., Sowa T., Schulte T., et al. Reactive oxygen species-activated Ca/calmodulin kinase IIdelta is required for late I(Na) augmentation leading to cellular Na and Ca overload. Circ Res 2011, 108:555-565.
55. Veldkamp M.W., Viswanathan P.C., Bezzina C., Baartscheer A., Wilde A.A., Balser J.R. Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel. Circ Res 2000, 86:E91-E97.
56. Bezzina C., Veldkamp M.W., van Den Berg M.P., Postma A.V., Rook M.B., Viersma J.W., et al. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999, 85:1206-1213.
57. Vohra J. Diagnosis and management of Brugada syndrome. Heart Lung Circ 2011, 20:751-756.
58. Sossalla S., Maurer U., Schotola H., Hartmann N., Didie M., Zimmermann W.H., et al. Diastolic dysfunction and arrhythmias caused by overexpression of CaMKIIdelta(C) can be reversed by inhibition of late Na(+) current. Basic Res Cardiol 2011, 106:263-272.
59. Yao L., Fan P., Jiang Z., Viatchenko-Karpinski S., Wu Y., Kornyeyev D., et al. Nav1.5-dependent persistent Na+ influx activates CaMKII in rat ventricular myocytes and N1325S mice. Am J Physiol Cell Physiol 2011, 301:C577-C586.
60. Barsheshet A., Goldenberg I., J.O.U., Moss A.J., Jons C., Shimizu W., et al. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to beta-blocker therapy in type 1 long-QT syndrome. Circulation 2012, 125:1988-1996.
61. Wagner S., Hacker E., Grandi E., Weber S.L., Dybkova N., Sossalla S., et al. Ca/calmodulin kinase II differentially modulates potassium currents. Circ Arrhythm Electrophysiol 2009, 2:285-294.
62. Hagiwara K., Nunoki K., Ishii K., Abe T., Yanagisawa T. Differential inhibition of transient outward currents of Kv1.4 and Kv4.3 by endothelin. Biochem Biophys Res Commun 2003, 310:634-640.
63. Li J., Marionneau C., Zhang R., Shah V., Hell J.W., Nerbonne J.M., et al. Calmodulin kinase II inhibition shortens action potential duration by upregulation of K+ currents. Circ Res 2006, 99:1092-1099.
64. Beuckelmann D.J., Nabauer M., Erdmann E. Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure. Circ Res 1993, 73:379-385.
65. Grandi E., Puglisi J.L., Wagner S., Maier L.S., Severi S., Bers D.M. Simulation of Ca-calmodulin-dependent protein kinase II on rabbit ventricular myocyte ion currents and action potentials. Biophys J 2007, 93:3835-3847.