title: Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.
abstract: 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 °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 ∼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 ∼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.
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic. bebarova.lfmu@centrum.cz.
authors.forename: Markéta
authors.initials: M
authors.lastname: Bébarová
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Matejovič
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.|Institute of Thermomechanics-Branch Brno, Academy of Sciences of the Czech Republic, Technická 2, 616 69, Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Pásek
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hořáková
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.|Department of Molecular Biology and Pharmaceutical Biotechnology, Pharmaceutical Faculty, University of Veterinary and Pharmaceutical Sciences, Palackého tř. 1946/1,, 612 42, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hošek
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Milena
authors.initials: M
authors.lastname: Šimurdová
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Šimurda
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D016466:CHO Cells; D003198:Computer Simulation; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D018570:Risk Assessment; D014162:Transfection
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D000431:Ethanol; D000109:Acetylcholine
keywords: Dual effect; Ethanol; Inward rectifier; Kir3.1/3.4; Rat atrial cell model