Effect of ethanol on cardiac single sodium channel gating

Abstract

Alcohol in modest and higher doses has the potential to induce cardiac arrhythmias. The most famous alcohol-related arrhythmia is the “holiday heart syndrome”. Furthermore, there is a clear association between excessive alcohol consumption and the risk of sudden cardiac death. However, the acute effects of ethanol on arrhythmia induction are not well understood. The effect of ethanol on single cardiac sodium channels has not been studied yet. To elucidate the effect of ethanol on human cardiac sodium channels we performed a patch clamp study in HEK-293 cells overexpressing the human cardiac sodium channel. We used HEK-293 cells overexpressing the human cardiac sodium channel (Na 1.5). Single channel gating was investigated by the cell-attached patch clamp technique. Sodium channel currents were elicited by depolarizing pulses from −120 to −20 mV for a duration of 150 ms. Single channel availability, open probability and peak average current were assessed baseline and after addition of ethanol in increasing concentrations (0.50‰ (10.9 mM), 1.00‰ (21.7 mM), 2.00‰ (43.5 mM) and 4.00‰ (87.0 mM)). We found a concentration-dependent reduction of open probability which was statistically significant at 2.00‰ ethanol (66.5 ± 14% of control). At higher concentrations (4.00‰) also availability decreased to 66.5 ± 11.0% of control. This resulted in a significant decrease of peak average current at 2.00‰ and at 4.00‰ ethanol (61.8 ± 7.4 and 53.0 ± 8.2% of control). For the first time the present study demonstrates acute inhibitory effects of ethanol on single cardiac sodium channel gating and provides one potential mechanism for the well known clinical observation that ethanol triggers supraventricular and ventricular arrhythmias.