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(Circulation. 2000;101:2639.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Calcium-Activated Cl^- Current Contributes to Delayed Afterdepolarizations in Single Purkinje and Ventricular Myocytes

Arie O. Verkerk, PhD; Marieke W. Veldkamp, PhD; Lennart N. Bouman, PhD; Antoni C. G. van Ginneken, PhD

From the Department of Physiology, Academic Medical Center, University of Amsterdam, The Netherlands.

Correspondence to Arie Verkerk, Department of Physiology, University of Amsterdam, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail a.o.verkerk{at}amc.uva.nl

Background—The ionic mechanism underlying the transient inward current (I_ti), the current responsible for delayed afterdepolarizations (DADs), appears to be different in ventricular myocytes and Purkinje fibers. In ventricular myocytes, I_ti was ascribed to a Na⁺-Ca²⁺ exchange current, whereas in Purkinje fibers, it was additionally ascribed to a Cl^- current and a nonselective 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 ventricular 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 µmol/L norepinephrine. In both Purkinje and ventricular myocytes, I_ti was inward at negative potentials and outward at positive potentials. The anion blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) blocked outward I_ti completely but inward I_ti only slightly. The DIDS-sensitive component of I_ti was outwardly rectifying, with a reversal close to the reversal potential of Cl^- currents. Blockade of Na⁺-Ca²⁺ exchange by substitution of extracellular Na⁺ by equimolar Li⁺ abolished the DIDS-insensitive component of I_ti. DIDS reduced both DAD amplitude and triggered activity based on DADs.

Conclusions—In both Purkinje and ventricular myocytes, I_ti consists of 2 ionic mechanisms: a Cl^- current and a Na⁺-Ca²⁺ exchange current. Blockade of the Cl^- current may be potentially antiarrhythmogenic by lowering DAD amplitude and triggered activity based on DADs.

Key Words: currents • sodium • calcium • arrhythmia

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