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1 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6; and 2 Research Center and Department of Medicine, Montreal Heart Institute, Montreal, Quebec H1T 1C8 and University of Montreal, Montreal, Quebec, Canada H3C 3J7
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
(IKs) in PC repolarization, we studied PCs from canine ventricular false tendons with whole cell patch clamp (37°C). Typical IKs voltage- and time-dependent
properties were noted. Isoproterenol enhanced
IKs in a concentration-dependent fashion (EC50 ~ 30 nM), negatively shifted
IKs activation voltage dependence, and
accelerated IKs activation. Block of
IKs 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 
-adrenergic stimulation, IKs contributes little to PC repolarization;
however, -adrenergic stimulation increases the contribution of
IKs by increasing current amplitude,
accelerating IKs activation, and shifting
activation voltage toward the PC plateau voltage range.
IKs may therefore provide an important
"braking" function to limit PC APD prolongation in the presence of
-adrenergic stimulation.
ventricular arrhythmias; action potential; long Q-T syndrome
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