CaMKII signaling in heart diseases: Emerging role in diabetic cardiomyopathy

Hegyi, Bence; Bers, Donald M.; Bossuyt, Julie

doi:10.1016/j.yjmcc.2019.01.001

Cited by 111 publications

(107 citation statements)

References 244 publications

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“…On the other hand, there is substantial evidence to support the role of CaMKII-mediated phosphorylation in modulating RyR2 channel function in both health and disease [34,35,36,37,38]. Cooper et al (2013) also demonstrated that, in the presence of β-adrenergic agonist isoproterenol, RyR2 phosphorylation at CaMKII site Serine-2814 was significantly increased in ventricular myocytes from old rabbit hearts (four to six years old) in comparison to young (five to nine months old) [9].…”

Section: Intracellular Ca2+ Homeostasis In the Aged Heartmentioning

confidence: 99%

Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart

Hamilton

Terentyev

2019

IJMS

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Aging of the heart is associated with a blunted response to sympathetic stimulation, reduced contractility, and increased propensity for arrhythmias, with the risk of sudden cardiac death significantly increased in the elderly population. The altered cardiac structural and functional phenotype, as well as age-associated prevalent comorbidities including hypertension and atherosclerosis, predispose the heart to atrial fibrillation, heart failure, and ventricular tachyarrhythmias. At the cellular level, perturbations in mitochondrial function, excitation-contraction coupling, and calcium homeostasis contribute to this electrical and contractile dysfunction. Major determinants of cardiac contractility are the intracellular release of Ca2+ from the sarcoplasmic reticulum by the ryanodine receptors (RyR2), and the following sequestration of Ca2+ by the sarco/endoplasmic Ca2+-ATPase (SERCa2a). Activity of RyR2 and SERCa2a in myocytes is not only dependent on expression levels and interacting accessory proteins, but on fine-tuned regulation via post-translational modifications. In this paper, we review how aberrant changes in intracellular Ca2+ cycling via these proteins contributes to arrhythmogenesis in the aged heart.

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Section: Intracellular Ca2+ Homeostasis In the Aged Heartmentioning

confidence: 99%

Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart

Hamilton

Terentyev

2019

IJMS

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“…In addition to the phosphorylation by PKA, CaMKII-mediated phosphorylation increases the I Ca,L and SERCA (by removing the inhibitory effect of phospholamban on SERCA) and activates RyR. Simultaneous activation of I Ca,L , SERCA (increases SR Ca 2+ content), and RyR therefore increases the possibility of spontaneous Ca 2+ release (Maier and Bers, 2007;Hegyi et al, 2019). Experimental data confirmed that higher RyR Ca 2+ sensitivity alone is not sufficient to elicit spontaneous Ca 2+ release and that inhibition of CaMKII in a CPVT mouse model prevents arrhythmias (Venetucci et al, 2007;Liu et al, 2011a).…”

Section: Inherited Syndromes Catecholaminergic Polymorphic Ventriculamentioning

confidence: 99%

Calcium Handling Defects and Cardiac Arrhythmia Syndromes

et al. 2020

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Calcium ions (Ca 2+) play a major role in the cardiac excitation-contraction coupling. Intracellular Ca 2+ concentration increases during systole and falls in diastole thereby determining cardiac contraction and relaxation. Normal cardiac function also requires perfect organization of the ion currents at the cellular level to drive action potentials and to maintain action potential propagation and electrical homogeneity at the tissue level. Any imbalance in Ca 2+ homeostasis of a cardiac myocyte can lead to electrical disturbances. This review aims to discuss cardiac physiology and pathophysiology from the elementary membrane processes that can cause the electrical instability of the ventricular myocytes through intracellular Ca 2+ handling maladies to inherited and acquired arrhythmias. Finally, the paper will discuss the current therapeutic approaches targeting cardiac arrhythmias.

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“…In addition, CaMKII can be activated by oxidative stress through oxidation of Met281/Met282 and in the presence of hyperglycemia by glycosylation of Ser280 (198). Active CaMKII regulates several major components of cardiomyocyte calcium handling, such as LTCC, RyR2, SERCA2a, SLN and PLN (Table 2.2), and plays an important role in cardiac contraction (through the phosphorylation of MyBP-C and titin), gene transcription, intracellular trafficking, cellular energetics, hypertrophy, inflammation and cell death in a tightly controlled spatiotemporal manner (198)(199)(200). CaMKIImediated regulation involves direct phosphorylation of targets, as well as indirect regulation of reactive oxygen species, nitric oxide signaling, phosphatases and phosphodiesterases, intracellular trafficking and gene expression (185,199,201).…”

Section: Camkiimentioning

confidence: 99%

“…Active CaMKII regulates several major components of cardiomyocyte calcium handling, such as LTCC, RyR2, SERCA2a, SLN and PLN (Table 2.2), and plays an important role in cardiac contraction (through the phosphorylation of MyBP-C and titin), gene transcription, intracellular trafficking, cellular energetics, hypertrophy, inflammation and cell death in a tightly controlled spatiotemporal manner (198)(199)(200). CaMKIImediated regulation involves direct phosphorylation of targets, as well as indirect regulation of reactive oxygen species, nitric oxide signaling, phosphatases and phosphodiesterases, intracellular trafficking and gene expression (185,199,201). CaMKII-dependent phosphorylation of RyR2 is increased in transverse aortic constriction-induced HF and contributes to pathological SR calcium leak and HF progression (202,203).…”

Section: Camkiimentioning

confidence: 99%

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Integrative computational modeling of calcium handling and cardiac arrhythmias

Sutanto¹

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CaMKII signaling in heart diseases: Emerging role in diabetic cardiomyopathy

Cited by 111 publications

References 244 publications

Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart

Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart

Calcium Handling Defects and Cardiac Arrhythmia Syndromes

Integrative computational modeling of calcium handling and cardiac arrhythmias

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