Abstract
Cardiac K channels are critical determinants of cardiac excitability. In hypertrophied and failing myocardium, alterations in the expression and activity of voltage-gated K channels are frequently observed and contribute to the increased propensity for life-threatening arrhythmias. Thus, understanding the mechanisms of disturbed K channel regulation in heart failure (HF) is of critical importance. Amongst others, Ca/calmodulin-dependent protein kinase II (CaMKII) has been identified as an important regulator of K channel activity. In human HF but also various animal models, increased CaMKII expression and activity has been linked to deteriorated contractile function and arrhythmias. This review will discuss the current knowledge about CaMKII regulation of several K channels, its influence on action potential properties, dispersion of repolarization, and arrhythmias with special focus on HF.
Highlights
Heart failure (HF) is a leading cause of death in western countries (United States and Europe), (Neumann et al, 2009; Go et al, 2012; Nichols et al, 2013) and in developing countries like China (Hu et al, 2012)
Further evidence for a direct regulation of Ito,fast by calmodulin-dependent protein kinase II (CaMKII) comes from studies in rat ventricular myocyte lysates showing that CaMKII co-immunoprecipitates with both Kv4.3 and Kv4.2 (Colinas, 2006), and inhibition of CaMKII with KN-93 resulted in a significant acceleration of Ito inactivation even through recovery from inactivation was unaffected (Colinas, 2006)
SUMMARY While there is increasing evidence for an involvement of CaMKII in the regulation of K channels, many discrepancies are not yet understood. These discrepancies result from the great variability in the expression profile of K channels in different species and disease models
Summary
Reviewed by: Stephane Hatem, Pierre-and-Marie-Curie University, France Daniel C. Cardiac K channels are critical determinants of cardiac excitability. In hypertrophied and failing myocardium, alterations in the expression and activity of voltage-gated K channels are frequently observed and contribute to the increased propensity for life-threatening arrhythmias. Understanding the mechanisms of disturbed K channel regulation in heart failure (HF) is of critical importance. Ca/calmodulin-dependent protein kinase II (CaMKII) has been identified as an important regulator of K channel activity. In human HF and various animal models, increased CaMKII expression and activity has been linked to deteriorated contractile function and arrhythmias. This review will discuss the current knowledge about CaMKII regulation of several K channels, its influence on action potential properties, dispersion of repolarization, and arrhythmias with special focus on HF
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