Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine



Year of publication 2016
Type Article in Periodical
Magazine / Source Naunyn-Schmiedeberg's Archives of Pharmacology
MU Faculty or unit

Faculty of Medicine

Doi http://dx.doi.org/10.1007/s00210-016-1265-z
Field Physiology
Keywords Ethanol; Inward rectifier; Dual effect; Kir3.1/3.4; Rat atrial cellmodel
Description Alcohol intoxication tends to induce arrhythmias, most often the atrial fibrillation. To elucidate arrhythmogenic mechanisms related to alcohol consumption, the effect of ethanol on main components of the ionic membrane current is investigated step by step. Considering limited knowledge, we aimed to examine the effect of clinically relevant concentrations of ethanol (0.8-80 mM) on acetylcholine-sensitive inward rectifier potassium current I (K(Ach)). Experiments were performed by the whole-cell patch clamp technique at 23 +/- 1 A degrees C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of I (K(Ach)) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of I (K(Ach)) was significantly increased by ethanol with the maximum effect (an increase by similar to 100 %) between 8 and 20 mM. The changes were comparable in rat and guinea-pig atrial myocytes and also in expressed human Kir3.1/3.4 channels (i.e., structural correlate of I (K(Ach))). In the case of the acetylcholine-induced component of I (K(Ach)), a dual ethanol effect was apparent with a striking heterogeneity of changes in individual cells. The effect correlated with the current magnitude in control: the current was increased by eth-anol in the cells showing small current in control and vice versa. The average effect peaked at 20 mM ethanol (an increase of the current by similar to 20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of I (K(Ach)) even in concentrations corresponding to light alcohol consumption.
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