Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes.
OBJECTIVE
Even though alcohol intoxication is often linked to arrhythmias, data describing ethanol effect on cardiac ionic channels are rare. In addition, ethanol is used as a solvent of hydrophobic compounds in experimental studies. We investigated changes of the action potential (AP) configuration and main ionic membrane currents in rat cardiomyocytes under 20-1500 m(M) ethanol.


METHODS
Experiments were performed on enzymatically isolated rat right ventricular myocytes using the whole cell patch-clamp technique at room temperature.


RESULTS
Ethanol reversibly decelerated the upstroke velocity and decreased AP amplitude and duration at 0.2 and 3 Hz. The fast sodium current I(Na) , l-type calcium current I(Ca) and transient outward potassium current I(to) were reversibly inhibited in a concentration-dependent manner (50% inhibition at 446 ± 12, 553 ± 49 and 1954 ± 234 m(M), respectively, with corresponding Hill coefficients 3.1 ± 0.3, 1.1 ± 0.2 and 0.9 ± 0.1). Suppression of I(Na) and I(Ca) magnitude was slightly voltage dependent. The effect on I(Ca) and I(to) was manifested mainly as an acceleration of their apparent inactivations with a decreased slow and fast time constant respectively. As a consequence of marked differences in n(H) , sensitivity of the currents to ethanol at 10% inhibition decreases in the following order: I(Ca) (75 mm, 3.5‰), I(to) (170 m(M), 7.8‰) and I(Na) (220 m(M), 10.1‰).


CONCLUSIONS
Our results suggest a slight inhibition of all the currents at ethanol concentrations relevant to deep alcohol intoxication. The concentration dependence measured over a wide range may serve as a guideline when using ethanol as a solvent.
Bébarová
M
M
Department of Physiology, Masaryk University, Brno - Bohunice, Czech Republic. bebarova.lfmu@centrum.cz
Matejovič
P
P
Pásek
M
M
Ohlídalová
D
D
Jansová
D
D
Simurdová
M
M
Simurda
J
J
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D012997:Solvents
D002492:Central Nervous System Depressants; D007473:Ion Channels; D012997:Solvents; D000431:Ethanol; D012964:Sodium; D011188:Potassium; D002118:Calcium