Ethanol inhibition of Ca2+ and Na+ currents in the guinea-pig heart

Abstract

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.