Calcium-activated Cl- current contributes to delayed afterdepolarizations in single Purkinje and ventricular myocytes

Background-The ionic mechanism underlying the transient inward current (I-t i), the current responsible for delayed afterdepolarizations (DADs), appear s to be different in ventricular myocytes and Purkinje fibers. In ventricul ar myocytes, I-ti was ascribed to a Na+-Ca2+ exchange current, whereas in P urkinje fibers, it was additionally ascribed to a Cl- current and a nonsele ctive cation current, If Cl- current contributes to I-ti and thus to DADs, Cl- current blockade may be potentially antiarrhythmogenic. In this study, we investigated the ionic nature of I-ti in single sheep Purkinje and ventr icular myocytes and the effects of Cl- current blockade on DADs. Methods and Results-In whole-cell patch-clamp experiments, I-ti was induced by repetitive depolarizations from -93 to +37 mV in the presence of 1 mu m ol/L norepinephrine. In both Purkinje and ventricular myocytes, I-ti was in ward at negative potentials and outward at positive potentials. The anion b locker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) blocked ou tward Ii completely but inward Ii only slightly. The DIDS-sensitive compone nt of Ii was outwardly rectifying, with a reversal close to the reversal po tential of Cl- currents. Blockade of Na+-Ca2+ exchange by substitution of e xtracellular Na+ by equimolar Li+ abolished the DIDS-insensitive component of I-ti. DIDS reduced both DAD amplitude and triggered activity based on DA Ds. Conclusions-In both Purkinje and ventricular myocytes, I-ti consists of 2 i onic mechanisms: a Cl- current and a Na+-Ca2+ exchange current. Blockade of the Cl- current may be potentially antiarrhythmogenic by lowering DAD ampl itude and triggered activity based on DADs.