The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias

Bibliography

• Zhang T, Brown JH. Role of Ca2+/calmodulin-dependent protein kinase II in cardiac hypertrophy and heart failure. Cardiovasc Res 2004;63:476-86
   PubMed Web of Science ®Google Scholar
• Rellos P, Pike AC, Niesen FH, et al. Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. PLoS Biol 2010;8:e1000426
   PubMed Web of Science ®Google Scholar
• Erickson JR, Joiner ML, Guan X, et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 2008;133:462-74
   PubMed Web of Science ®Google Scholar
• Kuret J, Schulman H. Mechanism of autophosphorylation of the multifunctional Ca2+/calmodulin-dependent protein kinase. J Biol Chem 1985;260:6427-33
   PubMed Web of Science ®Google Scholar
• Meyer T, Hanson PI, Stryer L, Schulman H. Calmodulin trapping by calcium-calmodulin-dependent protein kinase. Science 1992;256:1199-202
   PubMed Web of Science ®Google Scholar
• Wagner S, Ruff HM, Weber SL, 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;108:555-65
   PubMed Web of Science ®Google Scholar
• Colbran RJ. Inactivation of Ca2+/calmodulin-dependent protein kinase II by basal autophosphorylation. J Biol Chem 1993;268:7163-70
   PubMed Web of Science ®Google Scholar
• Hund TJ, Koval OM, Li J, et al. A beta(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest 2010;120:3508-19
   PubMed Web of Science ®Google Scholar
• El-Haou S, Balse E, Neyroud N, et al. Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes. Circ Res 2009;104:758-69
   PubMed Web of Science ®Google Scholar
• Couchonnal LF, Anderson ME. The role of calmodulin kinase II in myocardial physiology and disease. Physiology (Bethesda) 2008;23:151-9
   PubMed Web of Science ®Google Scholar
• Zhao Z, Wen H, Fefelova N, et al. Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents? Am J Physiol Heart Circ Physiol 2012;302:H1636-44
   PubMed Web of Science ®Google Scholar
• Nemec J, Kim JJ, Gabris B, Salama G. Calcium oscillations and T-wave lability precede ventricular arrhythmias in acquired long QT type 2. Heart Rhythm 2010;7:1686-94
   PubMed Web of Science ®Google Scholar
• Weiss JN, Garfinkel A, Karagueuzian HS, et al. Early afterdepolarizations and cardiac arrhythmias. Heart Rhythm 2010;7:1891-9
   PubMed Web of Science ®Google Scholar
• Venetucci LA, Trafford AW, O'Neill SC, Eisner DA. The sarcoplasmic reticulum and arrhythmogenic calcium release. Cardiovasc Res 2008;77:285-92
   PubMed Web of Science ®Google Scholar
• McCarron JG, McGeown JG, Reardon S, et al. Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II. Nature 1992;357:74-7
   PubMed Web of Science ®Google Scholar
• Yuan W, Bers DM. Ca-dependent facilitation of cardiac Ca current is due to Ca-calmodulin-dependent protein kinase. Am J Physiol 1994;267:H982-93
   Google Scholar
• Anderson ME, Braun AP, Schulman H, Premack BA. Multifunctional Ca2+/calmodulin-dependent protein kinase mediates Ca(2+)-induced enhancement of the L-type Ca2+ current in rabbit ventricular myocytes. Circ Res 1994;75:854-61
   PubMed Web of Science ®Google Scholar
• Dzhura I, Wu Y, Colbran RJ, et al. Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol 2000;2:173-7
   PubMed Web of Science ®Google Scholar
• Yue DT, Herzig S, Marban E. Beta-adrenergic stimulation of calcium channels occurs by potentiation of high-activity gating modes. Proc Natl Acad Sci USA 1990;87:753-7
   PubMed Web of Science ®Google Scholar
• Hess P, Lansman JB, Tsien RW. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature 1984;311:538-44
   PubMed Web of Science ®Google Scholar
• Anderson ME, Brown JH, Bers DM. CaMKII in myocardial hypertrophy and heart failure. J Mol Cell Cardiol 2011;51:468-73
   PubMed Web of Science ®Google Scholar
• Lee TS, Karl R, Moosmang S, et al. Calmodulin kinase II is involved in voltage-dependent facilitation of the L-type Cav1.2 calcium channel: identification of the phosphorylation sites. J Biol Chem 2006;281:25560-7
   PubMed Web of Science ®Google Scholar
• Grueter CE, Abiria SA, Dzhura I, et al. L-type Ca2+ channel facilitation mediated by phosphorylation of the beta subunit by CaMKII. Mol Cell 2006;23:641-50
   PubMed Web of Science ®Google Scholar
• Koval OM, Guan X, Wu Y, et al. CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations. Proc Natl Acad Sci USA 2010;107:4996-5000
   PubMed Web of Science ®Google Scholar
• Blaich A, Welling A, Fischer S, et al. Facilitation of murine cardiac L-type Ca(v)1.2 channel is modulated by calmodulin kinase II-dependent phosphorylation of S1512 and S1570. Proc Natl Acad Sci USA 2010;107:10285-9
   PubMed Web of Science ®Google Scholar
• Ronkainen JJ, Hanninen SL, Korhonen T, et al. Ca2+-calmodulin-dependent protein kinase II represses cardiac transcription of the L-type calcium channel alpha(1C)-subunit gene (Cacna1c) by DREAM translocation. J Physiol 2011;589:2669-86
   PubMed Web of Science ®Google Scholar
• Bers DM. Altered cardiac myocyte Ca regulation in heart failure. Physiology (Bethesda) 2006;21:380-7
   PubMed Web of Science ®Google Scholar
• Guo J, Duff HJ. Calmodulin kinase II accelerates L-type Ca2+ current recovery from inactivation and compensates for the direct inhibitory effect of [Ca2+]i in rat ventricular myocytes. J Physiol 2006;574:509-18
   PubMed Web of Science ®Google Scholar
• Wagner S, Dybkova N, Rasenack EC, et al. Ca2+/calmodulin-dependent protein kinase II regulates cardiac Na+ channels. J Clin Invest 2006;116:3127-38
   PubMed Web of Science ®Google Scholar
• Zhang T, Maier LS, Dalton ND, et al. The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circ Res 2003;92:912-19
   PubMed Web of Science ®Google Scholar
• Aiba T, Hesketh GG, Liu T, et al. Na+ channel regulation by Ca2+/calmodulin and Ca2+/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes. Cardiovasc Res 2010;85:454-63
   PubMed Web of Science ®Google Scholar
• Yoon JY, Ho WK, Kim ST, Cho H. Constitutive CaMKII activity regulates Na+ channel in rat ventricular myocytes. J Mol Cell Cardiol 2009;47:475-84
   PubMed Web of Science ®Google Scholar
• Koval OM, Snyder JS, Wolf RM, et al. CaMKII-based regulation of voltage-gated Na+ channel in cardiac disease. Circulation 2012;126:2084-94
   PubMed Web of Science ®Google Scholar
• Ashpole NM, Herren AW, Ginsburg KS, et al. Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates cardiac sodium channel NaV1.5 gating by multiple phosphorylation sites. J Biol Chem 2012;287:19856-69
   PubMed Web of Science ®Google Scholar
• Veldkamp MW, Viswanathan PC, Bezzina C, et al. Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel. Circ Res 2000;86:E91-7
   PubMed Web of Science ®Google Scholar
• Nerbonne JM. Repolarizing cardiac potassium channels: multiple sites and mechanisms for CaMKII-mediated regulation. Heart Rhythm 2011;8:938-41
   PubMed Web of Science ®Google Scholar
• Li J, Marionneau C, Zhang R, et al. Calmodulin kinase II inhibition shortens action potential duration by upregulation of K+ currents. Circ Res 2006;99:1092-9
   PubMed Web of Science ®Google Scholar
• Xiao L, Coutu P, Villeneuve LR, et al. Mechanisms underlying rate-dependent remodeling of transient outward potassium current in canine ventricular myocytes. Circ Res 2008;103:733-42
   Google Scholar
• Wagner S, Hacker E, Grandi E, et al. Ca/calmodulin kinase II differentially modulates potassium currents. Circ Arrhythm Electrophysiol 2009;2:285-94
   PubMed Web of Science ®Google Scholar
• Guo W, Xu H, London B, Nerbonne JM. Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes. J Physiol 1999;521 Pt 3:587-99
   PubMed Web of Science ®Google Scholar
• Sergeant GP, Ohya S, Reihill JA, et al. Regulation of Kv4.3 currents by Ca2+/calmodulin-dependent protein kinase II. Am J Physiol Cell Physiol 2005;288:C304-13
   Web of Science ®Google Scholar
• Tessier S, Karczewski P, Krause EG, et al. Regulation of the transient outward K(+) current by Ca(2+)/calmodulin-dependent protein kinases II in human atrial myocytes. Circ Res 1999;85:810-19
   PubMed Web of Science ®Google Scholar
• Ledoux J, Chartier D, Leblanc N. Inhibitors of calmodulin-dependent protein kinase are nonspecific blockers of voltage-dependent K+ channels in vascular myocytes. J Pharmacol Exp Ther 1999;290:1165-74
   PubMed Web of Science ®Google Scholar
• Anderson ME, Braun AP, Wu Y, et al. 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
   PubMed Web of Science ®Google Scholar
• Lokuta AJ, Rogers TB, Lederer WJ, Valdivia HH. Modulation of cardiac ryanodine receptors of swine and rabbit by a phosphorylation-dephosphorylation mechanism. J Physiol 1995;487(Pt 3):609-22
   PubMed Web of Science ®Google Scholar
• Witcher DR, Kovacs RJ, Schulman H, et al. Unique phosphorylation site on the cardiac ryanodine receptor regulates calcium channel activity. J Biol Chem 1991;266:11144-52
   PubMed Web of Science ®Google Scholar
• Wehrens XH, Lehnart SE, Reiken SR, Marks AR. Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor. Circ Res 2004;94:e61-70
   PubMed Web of Science ®Google Scholar
• Kohlhaas M, Seidler T, Zibrova D, et al. Increased sarcoplasmic reticulum calcium leak but unaltered contractility by acute CaMKII overexpression in isolated rabbit cardiac myocytes. Circ Res 2006;98:235-44
   PubMed Web of Science ®Google Scholar
• Maier LS, Zhang T, Chen L, et al. Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release. Circ Res 2003;92:904-11
   PubMed Web of Science ®Google Scholar
• Curran J, Hinton MJ, Rios E, et al. Beta-adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac myocytes is mediated by calcium/calmodulin-dependent protein kinase. Circ Res 2007;100:391-8
   PubMed Web of Science ®Google Scholar
• Ai X, Curran JW, Shannon TR, et al. Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. Circ Res 2005;97:1314-22
   PubMed Web of Science ®Google Scholar
• van Oort RJ, McCauley MD, Dixit SS, et al. Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure. Circulation 2010;122:2669-79
   PubMed Web of Science ®Google Scholar
• Respress JL, van Oort RJ, Li N, et al. Role of RyR2 phosphorylation at S2814 during heart failure progression. Circ Res 2012;110:1474-83
   PubMed Web of Science ®Google Scholar
• Curran J, Brown KH, Santiago DJ, et al. 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
   PubMed Web of Science ®Google Scholar
• Toyofuku T, Curotto Kurzydlowski K, Narayanan N, MacLennan DH. Identification of Ser38 as the site in cardiac sarcoplasmic reticulum Ca(2+)-ATPase that is phosphorylated by Ca2+/calmodulin-dependent protein kinase. J Biol Chem 1994;269:26492-6
   PubMed Web of Science ®Google Scholar
• Odermatt A, Kurzydlowski K, MacLennan DH. The vmax of the Ca2+-ATPase of cardiac sarcoplasmic reticulum (SERCA2a) is not altered by Ca2+/calmodulin-dependent phosphorylation or by interaction with phospholamban. J Biol Chem 1996;271:14206-13
   PubMed Web of Science ®Google Scholar
• Lu YM, Huang J, Shioda N, et al. CaMKIIdeltaB mediates aberrant NCX1 expression and the imbalance of NCX1/SERCA in transverse aortic constriction-induced failing heart. PLoS One 2011;6:e24724
   Web of Science ®Google Scholar
• Mani SK, Egan EA, Addy BK, et al. Beta-Adrenergic receptor stimulated Ncx1 upregulation is mediated via a CaMKII/AP-1 signaling pathway in adult cardiomyocytes. J Mol Cell Cardiol 2010;48:342-51
   PubMed Web of Science ®Google Scholar
• Khoo MS, Li J, Singh MV, et al. Death, cardiac dysfunction, and arrhythmias are increased by calmodulin kinase II in calcineurin cardiomyopathy. Circulation 2006;114:1352-9
   PubMed Web of Science ®Google Scholar
• Sag CM, Wadsack DP, Khabbazzadeh S, et al. Calcium/calmodulin-dependent protein kinase II contributes to cardiac arrhythmogenesis in heart failure. Circ Heart Fail 2009;2:664-75
   PubMed Web of Science ®Google Scholar
• Wu Y, Temple J, Zhang R, et al. Calmodulin kinase II and arrhythmias in a mouse model of cardiac hypertrophy. Circulation 2002;106:1288-93
   PubMed Web of Science ®Google Scholar
• Tsuji Y, Hojo M, Voigt N, et al. Ca(2+)-related signaling and protein phosphorylation abnormalities play central roles in a new experimental model of electrical storm. Circulation 2011;123:2192-203
   PubMed Web of Science ®Google Scholar
• Qi X, Yeh YH, Chartier D, et al. The calcium/calmodulin/kinase system and arrhythmogenic afterdepolarizations in bradycardia-related acquired long-QT syndrome. Circ Arrhythm Electrophysiol 2009;2:295-304
   PubMed Web of Science ®Google Scholar
• Bourgonje VJ, Schoenmakers M, Beekman JD, et al. Relevance of calmodulin/CaMKII activation for arrhythmogenesis in the AV block dog. Heart Rhythm 2012;9:1875-83
   PubMed Web of Science ®Google Scholar
• Neef S, Dybkova N, Sossalla S, 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;106:1134-44
   PubMed Web of Science ®Google Scholar
• Li N, Wang T, Wang W, et al. Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circ Res 2012;110:465-70
   PubMed Web of Science ®Google Scholar
• Chelu MG, Sarma S, Sood S, et al. Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice. J Clin Invest 2009;119:1940-51
   PubMed Web of Science ®Google Scholar
• Voigt N, Li N, Wang Q, et al. Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation 2012;125:2059-70
   PubMed Web of Science ®Google Scholar
• Liu N, Ruan Y, Denegri M, et al. Calmodulin kinase II inhibition prevents arrhythmias in RyR2(R4496C+/-) mice with catecholaminergic polymorphic ventricular tachycardia. J Mol Cell Cardiol 2011;50:214-22
   PubMed Web of Science ®Google Scholar
• Degrande S, Nixon D, Koval O, et al. CaMKII inhibition rescues proarrhythmic phenotypes in the model of human ankyrin-B syndrome. Heart Rhythm 2012;9:2034-41
   PubMed Web of Science ®Google Scholar
• Thiel WH, Chen B, Hund TJ, et al. Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. Circulation 2008;118:2225-34
   PubMed Web of Science ®Google Scholar
• Valverde CA, Mundina-Weilenmann C, Reyes M, et al. Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart. Cardiovasc Res 2006;70:335-45
   PubMed Web of Science ®Google Scholar
• Hoch B, Meyer R, Hetzer R, et al. Identification and expression of delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium. Circ Res 1999;84:713-21
   PubMed Web of Science ®Google Scholar
• Joiner ML, Koval OM, Li J, et al. CaMKII determines mitochondrial stress responses in heart. Nature 2012;491:269-73
   PubMed Web of Science ®Google Scholar
• Yang Y, Zhu WZ, Joiner ML, et al. Calmodulin kinase II inhibition protects against myocardial cell apoptosis in vivo. Am J Physiol Heart Circ Physiol 2006;291:H3065-75
   Web of Science ®Google Scholar
• Salas MA, Valverde CA, Sanchez G, et al. The signalling pathway of CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury. J Mol Cell Cardiol 2010;48:1298-306
   PubMed Web of Science ®Google Scholar
• Toko H, Takahashi H, Kayama Y, et al. Ca2+/calmodulin-dependent kinase IIdelta causes heart failure by accumulation of p53 in dilated cardiomyopathy. Circulation 2010;122:891-9
   PubMed Web of Science ®Google Scholar
• Singh MV, Kapoun A, Higgins L, et al. Ca2+/calmodulin-dependent kinase II triggers cell membrane injury by inducing complement factor B gene expression in the mouse heart. J Clin Invest 2009;119:986-96
   PubMed Web of Science ®Google Scholar
• Ling H, Gray CB, Zambon AC, et al. Ca2+/Calmodulin-dependent protein kinase II delta mediates myocardial ischemia/reperfusion injury through nuclear factor-kappaB. Circ Res 2013;112:935-44
   PubMed Web of Science ®Google Scholar
• Zhang R, Khoo MS, Wu Y, et al. Calmodulin kinase II inhibition protects against structural heart disease. Nat Med 2005;11:409-17
   PubMed Web of Science ®Google Scholar
• He BJ, Joiner ML, Singh MV, et al. Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nat Med 2011;17:1610-18
   PubMed Web of Science ®Google Scholar
• Kannel WB, Doyle JT, McNamara PM, et al. Precursors of sudden coronary death. Factors related to the incidence of sudden death. Circulation 1975;51:606-13
   PubMed Web of Science ®Google Scholar
• Frey N, Olson EN. Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 2003;65:45-79
   PubMed Web of Science ®Google Scholar
• Mishra S, Ling H, Grimm M, et al. Cardiac hypertrophy and heart failure development through Gq and CaM kinase II signaling. J Cardiovasc Pharmacol 2010;56:598-603
   PubMed Web of Science ®Google Scholar
• D'Angelo DD, Sakata Y, Lorenz JN, et al. Transgenic Galphaq overexpression induces cardiac contractile failure in mice. Proc Natl Acad Sci USA 1997;94:8121-6
   PubMed Web of Science ®Google Scholar
• Zhu W, Zou Y, Shiojima I, et al. Ca2+/calmodulin-dependent kinase II and calcineurin play critical roles in endothelin-1-induced cardiomyocyte hypertrophy. J Biol Chem 2000;275:15239-45
   PubMed Web of Science ®Google Scholar
• Wu X, Zhang T, Bossuyt J, et al. Local InsP3-dependent perinuclear Ca2+ signaling in cardiac myocyte excitation-transcription coupling. J Clin Invest 2006;116:675-82
   PubMed Web of Science ®Google Scholar
• O-Uchi J, Komukai K, Kusakari Y, et al. Alpha1-adrenoceptor stimulation potentiates L-type Ca2+ current through Ca2+/calmodulin-dependent PK II (CaMKII) activation in rat ventricular myocytes. Proc Natl Acad Sci USA 2005;102:9400-5
   PubMed Web of Science ®Google Scholar
• Zhu WZ, Wang SQ, Chakir K, et al. Linkage of beta1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II. J Clin Invest 2003;111:617-25
   PubMed Web of Science ®Google Scholar
• Sucharov CC, Mariner PD, Nunley KR, et al. A beta1-adrenergic receptor CaM kinase II-dependent pathway mediates cardiac myocyte fetal gene induction. Am J Physiol Heart Circ Physiol 2006;291:H1299-308
   Web of Science ®Google Scholar
• Hoen S, Mazoit JX, Asehnoune K, et al. Hydrocortisone increases the sensitivity to alpha1-adrenoceptor stimulation in humans following hemorrhagic shock. Crit Care Med 2005;33:2737-43
   PubMed Web of Science ®Google Scholar
• Lin SL, Johnson-Farley NN, Lubinsky DR, Cowen DS. Coupling of neuronal 5-HT7 receptors to activation of extracellular-regulated kinase through a protein kinase A-independent pathway that can utilize Epac. J Neurochem 2003;87:1076-85
   PubMed Web of Science ®Google Scholar
• Ramirez MT, Zhao XL, Schulman H, Brown JH. The nuclear deltaB isoform of Ca2+/calmodulin-dependent protein kinase II regulates atrial natriuretic factor gene expression in ventricular myocytes. J Biol Chem 1997;272:31203-8
   PubMed Web of Science ®Google Scholar
• Zhang T, Johnson EN, Gu Y, et al. The cardiac-specific nuclear delta(B) isoform of Ca2+/calmodulin-dependent protein kinase II induces hypertrophy and dilated cardiomyopathy associated with increased protein phosphatase 2A activity. J Biol Chem 2002;277:1261-7
   PubMed Web of Science ®Google Scholar
• Zhang T, Kohlhaas M, Backs J, et al. CaMKIIdelta isoforms differentially affect calcium handling but similarly regulate HDAC/MEF2 transcriptional responses. J Biol Chem 2007;282:35078-87
   PubMed Web of Science ®Google Scholar
• Backs J, Song K, Bezprozvannaya S, et al. CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest 2006;116:1853-64
   PubMed Web of Science ®Google Scholar
• Ling H, Zhang T, Pereira L, et al. Requirement for Ca2+/calmodulin-dependent kinase II in the transition from pressure overload-induced cardiac hypertrophy to heart failure in mice. J Clin Invest 2009;119:1230-40
   PubMed Web of Science ®Google Scholar
• Grimm M, Ling H, Brown JH. Crossing signals: relationships between beta-adrenergic stimulation and CaMKII activation. Heart Rhythm 2011;8:1296-8
   PubMed Web of Science ®Google Scholar
• Backs J, Backs T, Neef S, et al. The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc Natl Acad Sci USA 2009;106:2342-7
   PubMed Web of Science ®Google Scholar
• Dunlay SM, Shah ND, Shi Q, et al. Lifetime costs of medical care after heart failure diagnosis. Circ Cardiovasc Qual Outcomes 2011;4:68-75
   PubMed Web of Science ®Google Scholar
• Zima AV, Blatter LA. Redox regulation of cardiac calcium channels and transporters. Cardiovasc Res 2006;71:310-21
   PubMed Web of Science ®Google Scholar
• Bers DM. Cardiac excitation-contraction coupling. Nature 2002;415:198-205
   PubMed Web of Science ®Google Scholar
• Piacentino V III, Weber CR, Chen X, et al. Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circ Res 2003;92:651-8
   PubMed Web of Science ®Google Scholar
• Mattiazzi A, Kranias EG. CaMKII regulation of phospholamban and SR Ca2+ load. Heart Rhythm 2011;8:784-7
   PubMed Web of Science ®Google Scholar
• Wu Y, Shintani A, Grueter C, et al. Suppression of dynamic Ca(2+) transient responses to pacing in ventricular myocytes from mice with genetic calmodulin kinase II inhibition. J Mol Cell Cardiol 2006;40:213-23
   PubMed Web of Science ®Google Scholar
• Maier LS, Bers DM. Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart. Cardiovasc Res 2007;73:631-40
   PubMed Web of Science ®Google Scholar
• Zhang T, Guo T, Mishra S, et al. Phospholamban ablation rescues sarcoplasmic reticulum Ca(2+) handling but exacerbates cardiac dysfunction in CaMKIIdelta(C) transgenic mice. Circ Res 2010;106:354-62
   PubMed Web of Science ®Google Scholar
• Wehrens XH. CaMKII regulation of the cardiac ryanodine receptor and sarcoplasmic reticulum calcium release. Heart Rhythm 2011;8:323-5
   PubMed Web of Science ®Google Scholar
• Kushnir A, Shan J, Betzenhauser MJ, et al. Role of CaMKIIdelta phosphorylation of the cardiac ryanodine receptor in the force frequency relationship and heart failure. Proc Natl Acad Sci USA 2010;107:10274-9
   PubMed Web of Science ®Google Scholar
• Westenbrink BD, Ling H, Miyamoto S, et al. Abstract 18574: mitochondrial Reprogramming By Camkii{delta} Underlies Gq-induced Cardiomyopathy. Circulation 2012;126:A18574
   Web of Science ®Google Scholar
• Swaminathan PD, Purohit A, Hund TJ, Anderson ME. Calmodulin-dependent protein kinase II: linking heart failure and arrhythmias. Circ Res 2012;110:1661-77
   PubMed Web of Science ®Google Scholar
• Noble D, Garny A, Noble PJ. How the Hodgkin-Huxley equations inspired the Cardiac Physiome Project. J Physiol 2012;590:2613-28
   PubMed Web of Science ®Google Scholar
• Saucerman JJ, Brunton LL, Michailova AP, McCulloch AD. Modeling beta-adrenergic control of cardiac myocyte contractility in silico. J Biol Chem 2003;278:47997-8003
   PubMed Web of Science ®Google Scholar
• Saucerman JJ, McCulloch AD. Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation. Prog Biophys Mol Biol 2004;85:261-78
   PubMed Web of Science ®Google Scholar
• Saucerman JJ, Healy SN, Belik ME, et al. Proarrhythmic consequences of a KCNQ1 AKAP-binding domain mutation: computational models of whole cells and heterogeneous tissue. Circ Res 2004;95:1216-24
   PubMed Web of Science ®Google Scholar
• Saucerman JJ, Zhang J, Martin JC, et al. Systems analysis of PKA-mediated phosphorylation gradients in live cardiac myocytes. Proc Natl Acad Sci USA 2006;103:12923-8
   PubMed Web of Science ®Google Scholar
• Saucerman JJ, Bers DM. Calmodulin mediates differential sensitivity of CaMKII and calcineurin to local Ca2+ in cardiac myocytes. Biophys J 2008;95:4597-612
   PubMed Web of Science ®Google Scholar
• Hashambhoy YL, Greenstein JL, Winslow RL. Role of CaMKII in RyR leak, EC coupling and action potential duration: a computational model. J Mol Cell Cardiol 2010;49:617-24
   PubMed Web of Science ®Google Scholar
• Soltis AR, Saucerman JJ. Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling. Biophys J 2010;99:2038-47
   PubMed Web of Science ®Google Scholar
• Heijman J, Volders PG, Westra RL, Rudy Y. Local control of beta-adrenergic stimulation: effects on ventricular myocyte electrophysiology and Ca(2+)-transient. J Mol Cell Cardiol 2011;50:863-71
   PubMed Web of Science ®Google Scholar
• Ryall KA, Holland DO, Delaney KA, et al. Network reconstruction and systems analysis of cardiac myocyte hypertrophy signaling. J Biol Chem 2012;287:42259-68
   PubMed Web of Science ®Google Scholar
• Anderson ME. Calmodulin kinase signaling in heart: an intriguing candidate target for therapy of myocardial dysfunction and arrhythmias. Pharmacol Ther 2005;106:39-55
   PubMed Web of Science ®Google Scholar
• Banyasz T, Szentandrassy N, Toth A, et al. Cardiac calmodulin kinase: a potential target for drug design. Curr Med Chem 2011;18:3707-13
   PubMed Web of Science ®Google Scholar
• Greene HL, Roden DM, Katz RJ, et al. The Cardiac Arrhythmia Suppression Trial: first CAST. then CAST-II. J Am Coll Cardiol 1992;19:894-8
   PubMed Web of Science ®Google Scholar
• McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:803-69
   PubMed Web of Science ®Google Scholar
• Luo M, Guan X, Luczak ED, et al. Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest 2013;123:1262-74
   PubMed Web of Science ®Google Scholar
• Swaminathan PD, Purohit A, Soni S, et al. Oxidized CaMKII causes cardiac sinus node dysfunction in mice. J Clin Invest 2011;121:3277-88
   PubMed Web of Science ®Google Scholar
• Hamdani N, Krysiak J, Kreusser MM, et al. Crucial role for Ca2(+)/calmodulin-dependent protein kinase-II in regulating diastolic stress of normal and failing hearts via titin phosphorylation. Circ Res 2013;112:664-74
   PubMed Web of Science ®Google Scholar
• Sossalla S, Fluschnik N, Schotola H, et al. Inhibition of elevated Ca2+/calmodulin-dependent protein kinase II improves contractility in human failing myocardium. Circ Res 2010;107:1150-61
   PubMed Web of Science ®Google Scholar
• Song YH, Cho H, Ryu SY, et al. L-type Ca(2+) channel facilitation mediated by H(2)O(2)-induced activation of CaMKII in rat ventricular myocytes. J Mol Cell Cardiol 2010;48:773-80
   PubMed Web of Science ®Google Scholar
• Rezazadeh S, Claydon TW, Fedida D. KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a calcium/calmodulin-dependent protein kinase II inhibitor, is a direct extracellular blocker of voltage-gated potassium channels. J Pharmacol Exp Ther 2006;317:292-9
   PubMed Web of Science ®Google Scholar
• Sumi M, Kiuchi K, Ishikawa T, et al. The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. Biochem Biophys Res Commun 1991;181:968-75
   PubMed Web of Science ®Google Scholar
• Peng W, Zhang Y, Zheng M, et al. Cardioprotection by CaMKII-deltaB is mediated by phosphorylation of heat shock factor 1 and subsequent expression of inducible heat shock protein 70. Circ Res 2010;106:102-10
   PubMed Web of Science ®Google Scholar
• Mishra S, Gray CB, Miyamoto S, et al. Location matters: clarifying the concept of nuclear and cytosolic CaMKII subtypes. Circ Res 2011;109:1354-62
   PubMed Web of Science ®Google Scholar
• Westenbrink BD, Gray CB, Xiang S, et al. Abstract 18536: CaMKII-{delta} splice variants exert differential effects on heart failure development and myocardial ischemia/reperfusion injury. Circulation 2012;126:A18536
   Web of Science ®Google Scholar