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

1989; American Physical Society; Volume: 256; Issue: 3 Linguagem: Inglês

10.1152/ajpcell.1989.256.3.c549

1522-1563

Frédérique Scamps, A. I. Undrovinas, Guy Vassort,

Nicotinic Acetylcholine Receptors Study

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.