The SCN5A gene encodes Nav1.5, which, as the cardiac voltage-gated Na+ channel's pore-forming α subunit, is crucial for the initiation and propagation of atrial and ventricular action potentials. The arrhythmogenic propensity of inherited SCN5A mutations implicates the Na+ channel in determining cardiomyocyte excitability under normal conditions. Cytosolic kinases have long been known to alter the kinetic profile of Nav1.5 inactivation via phosphorylation of specific residues. Recent substantiation of both the role of calmodulin-dependent kinase II (CaMKII) in modulating the properties of the Nav1.5 inactivation gate and the significant rise in oxidation-dependent autonomous CaMKII activity in structural heart disease has raised the possibility of a novel pathway for acquired arrhythmias - the CaMKII-Nav1.5 relationship. The aim of this review is to: (1) outline the relationship's translation from physiological adaptation to pathological vicious circle; and (2) discuss the relative merits of each of its components as pharmacological targets.
Keywords: Activator; Arrhythmogenesis; CaMKII; Inhibitor; Na(v)1.5; Oxidation; Target.
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