AJP - Cell Physiology, Vol 256, Issue 3 C549-C559, Copyright © 1989 by American Physiological Society

ARTICLES

Inhibition of ICa in single frog cardiac cells by quinidine, flecainide, ethmozin, and ethacizin

F. Scamps, A. Undrovinas and G. Vassort
Laboratoire de Physiologie Cellulaire Cardiaque, INSERM U-241, Universite Paris-Sud, Orsay, France.

The effects of four class I antiarrhythmic compounds on the Ca current (ICa), recorded with whole cell patch clamp in single isolated frog ventricular cells, were compared. Na and K currents were blocked by tetrodotoxin and Cs. Quinidine and flecainide induced an apparent tonic block with a 50% effective dose (ED50) at 10 and 20 microM, respectively; there was no clear use-dependent inhibition. Ethmozin and ethacizin, two phenothiazine derivatives, exhibited both tonic and use-dependent inhibition. Ethacizin was at least 10 times more potent than ethmozin; at 1 microM, it induced a 15% tonic block and 5, 35, and 42% use-dependent block at 0.125, 1, and 2 Hz, respectively. These compounds appeared only 3- to 10-fold less efficient on the ICa than on the Na current recorded in parallel experiments, with flecainide showing the largest different potency. All four compounds shifted the availability curves by a few millivolts toward hyperpolarization, had a clear voltage-dependent inhibition, and slowed reactivation, the latter effect being more marked with less negative holding potential. Consequently, the absence of use-dependence inhibition with quinidine and flecainide could be the consequence of a very fast association of the two compounds with the open channels that would be complete during the 200-ms depolarizing pulse. Since arrhythmias are frequently associated with tissue depolarization and can be related to Ca-dependent action potential and slow conduction, the inhibition of the ICa reported above should account, in part, both for the antiarrhythmic and the negative inotropic effects of these compounds.

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