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 regions of the canine ventricle. Sodium-calcium exchange current and voltage-dependent transient outward potassium current (IA) 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 (ICa) and a Ca(2+)-activated chloride current [ICl(Ca)]. ICl(Ca) was blocked by 200 microM 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 ICl(Ca) has a threshold of -20 mV and a peak at +40 mV. No evidence could be found for a Ca(2+)-activated potassium current or a Ca(2+)-activated nonspecific cation current under these conditions. ICl(Ca) 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, ICl(Ca) is likely to contribute to rate- and rhythm-dependent repolarization of the cardiac action potential.
Zygmunt
A C
AC
Masonic Medical Research Laboratory, Utica, New York 13501.
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D005260:Female; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008536:Meglumine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D013997:Time Factors
D015220:Calcium Channels; C004717:diacetylmonoxime; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000001:Calcimycin; D002110:Caffeine; D004533:Egtazic Acid; D008536:Meglumine; D015761:4-Aminopyridine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D003931:Diacetyl; D007545:Isoproterenol; D002122:Calcium Chloride; D002118:Calcium