Slow delayed rectifier current and repolarization in canine cardiac Purkinje cells

Although cardiac Purkinje cells (PCs) are believed to be the source of early afterdepolarizations generating ventricular tachyarrhythmias in long Q-T syndromes (LQTS), the ionic determinants of PC repolarization are incompletely known. To evaluate the role of the slow delayed rectifier current (I-Ks) in PC repolarization, we studied PCs from canine ventricular false tendons with whole cell patch clamp (37 degreesC). Typical IKs voltage- and time-dependent properties were noted. Isoproterenol enhanced I-Ks in a concentration- dependent fashion (EC50 similar to 30 nM), negatively shifted I-Ks activation voltage dependence, and accelerated I-Ks activation. Block of I-Ks with 293B did not alter PC action potential duration (APD) in the absence of isoproterenol; however, in the presence of isoproterenol, 293B significantly prolonged APD. We conclude that, without beta -adrenergic stimulation, I-Ks contributes little to PC repolarization; however, beta -adrenergic stimulation increases the contribution of I-Ks by increasing current amplitude, accelerating I-Ks activation, and shifting activation voltage toward the PC plateau voltage range. I-Ks may therefore provide an important "braking" function to limit PC APD prolongation in the presence of beta -adrenergic stimulation.