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

0462452 - ÚT 2017 RIV DE eng J - Journal Article
Bébarová, M. - Matejovič, P. - Pásek, Michal - Hořáková, Z. - Hošek, J. - Šimurdová, M. - Šimurda, J.
Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.
Naunyn-Schmiedeberg's Archives of Pharmacology. Roč. 389, č. 10 (2016), s. 1049-1058. ISSN 0028-1298. E-ISSN 1432-1912
Institutional support: RVO:61388998
Keywords : arrhythmias * atrial cardiomyocyte * inward rectifier potasssium current * ethanol * rat atrial cell model
Subject RIV: BO - Biophysics
Impact factor: 2.558, year: 2016

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 acetylcholinesensitive inward rectifier potassium current IK(Ach). Experiments were performed by the whole-cell patch clamp technique at 23 ± 1 °C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of IK(Ach) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of IK(Ach) was significantly increased by ethanol with the maximum effect (an increase by ∼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 IK(Ach)). In the case of the acetylcholine-induced component of IK(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 ethanol 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 ∼20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of IK(Ach) even in concentrations corresponding to light alcohol consumption.
Permanent Link: http://hdl.handle.net/11104/0265986