Modulation of Human Ether A Gogo Related Channels by CASQ2 Contributes to Etiology of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

The plateau phase of the ventricular action potential is the result of balanced Ca(2+) influx and K(+) efflux. The action potential is terminated by repolarizing K(+) currents. Under β-adrenergic stimulation, both the Ca(2+)-influx and the delayed rectifier K(+) currents I(K) are stimulated to adjust the cardiac action potential duration to the enhanced heart rate and to ascertain adequate increase in net Ca(2+) influx. Intracellularly, a Calsequestrin2 (CASQ2)-ryanodine receptor complex serves as the most effective Ca(2+) reservoir/release system to aid the control of intracellular Ca(2+) levels. Currently, it is unclear if disease-associated CASQ2 gene variants alter intracellular free Ca(2+) concentrations and if cardiac ion channels are affected by it.