INTRACELLULAR CALCIUM ACTIVATES A CHLORIDE CURRENT IN CANINE VENTRICULAR MYOCYTES

The contribution of chloride and potassium to the 4-aminopyridine (4-AP)-resistant transient outward current was investigated in dog cardiac myocytes. Whole cell currents were recorded at 37 degrees C in single cells dissociated from epicardial and midmyocardial dial regions of the canine ventricle. Sodium-calcium exchange current and voltage-dependent transient outward potassium current (I-A) were blocked in sodium-free solutions containing 2 mM 4-AP; sodium channels were inactivated by the -50-mV holding potential. When patch pipettes contained 0.4-0.8 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, voltage-clamp steps over the range -20 to +50 mV activated an inward calcium current (I-Ca) and a Ca2+-activated chloride current [I-Cl(Ca)] I-Cl(Ca), was blocked by 200 mu M 4,4'diisothiocyanostilbene-2,2'-disulfonic acid, 1 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), or reduction of external chloride. Independent of the presence of potassium, the reversal potential of the SITS-sensitive current varied with extracellular chloride, as predicted for a chloride-selective conductance. The bell-shaped current-voltage relation of I-Cl(Ca), has a threshold of -20 mV and a peak at +40 mV. No evidence could be found for a Ca2+-activated potassium current or a Ca2+-activated nonspecific cation current under these conditions. lace,, contributed to oscillatory inward currents at diastolic potentials in cells superfused by isoproterenol and high Ca2+, suggesting a role for this current in triggered arrhythmias associated with delayed afterdepolarizations. In the normal heart, I-Cl(Ca) is likely to contribute to rateand rhythm-dependent repolarization of the cardiac action potential.