ETHANOL INHIBITION OF CA2+ AND NA+ CURRENTS IN THE GUINEA-PIG HEART

The effects of ethanol on L-type Ca2+ and fast Na+ currents (I-Ca and I-Na, respectively) were examined using the whole-cell patch-clamp experiments on guinea-pig ventricular cells. At a clinically relevant concentration of 24 mM, ethanol slightly but significantly shortened the action potential duration, and reduced the I-Ca by 7 +/- 4% (mean +/- S.D.). This concentration of ethanol did not affect I-Na, but a lethal concentration of ethanol (80 mM) significantly inhibited I-Na by 13 +/- 5%. The voltage dependence of I-Na activation was not affected by ethanol, whereas the inhibitions of I-Ca by 80 mM ethanol and I-Na by 240 mM were both accompanied by a several mV shift in the channel availability curve toward more negative potentials, suggesting that the channels in the inactivated state are more susceptible to ethanol. The I-Ca inhibition by ethanol at clinically relevant concentrations could contribute to a negative inotropic effect, action potential shortening and development of arrhythmias, while the pathophysiological significance of ethanol inhibition of I-Na seems less important.