Calcium-activated chloride current in rabbit ventricular myocytes.
We have used the whole-cell patch-clamp technique to examine the ionic basis for a transient outward current in rabbit ventricular myocytes. High concentrations of intracellular calcium buffer prevented the current, isoproterenol increased it, and cadmium, nisoldipine, ryanodine, or caffeine blocked it. These data are consistent with a current that is calcium activated, by the calcium transient that causes contraction. The current was not blocked by external 4-aminopyridine or tetraethylammonium, and it was still present if external potassium was omitted and internal potassium was replaced by cesium. The current was absent when intracellular and extracellular chloride concentrations were drastically reduced, even when intracellular and extracellular potassium concentrations were normal. The current was blocked by the anion transport blockers 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and responded to extracellular chloride changes as expected for a chloride current. We used SITS and DIDS to define the voltage dependence of the transient outward current. The current first appeared at voltages positive to the threshold of the calcium current and declined as voltage approached the calcium reversal potential. Tail-current experiments suggested that the current rectified strongly in the outward direction. We propose that the 4-aminopyridine-resistant transient outward current of rabbit ventricular myocytes is a calcium-activated chloride current.
Zygmunt
A C
AC
Department of Physiology and Biophysics, University of Vermont, Burlington 05405.
Gibbons
W R
WR
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002712:Chlorides / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits
D002712:Chlorides; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D015761:4-Aminopyridine; D007545:Isoproterenol; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium