Ethanol inhibition of Ca2+ and Na+ currents in the guinea-pig heart.
The effects of ethanol on L-type Ca2+ and fast Na+ currents (ICa and INa, respectively) were examined using the whole-cell patch-clamp experiments on guinea-pig ventricular cells. At a clinically relevant concentration of 24 mM, ethanol slightly but significantly shortened the action potential duration, and reduced the ICa by 7 +/- 4% (mean +/- S.D.). This concentration of ethanol did not affect INa, but a lethal concentration of ethanol (80 mM) significantly inhibited INa by 13 +/- 5%. The voltage dependence of INa activation was not affected by ethanol, whereas the inhibitions of ICa by 80 mM ethanol and INa by 240 mM were both accompanied by a several mV shift in the channel availability curve toward more negative potentials, suggesting that the channels in the inactivated state are more susceptible to ethanol. The ICa inhibition by ethanol at clinically relevant concentrations could contribute to a negative inotropic effect, action potential shortening and development of arrhythmias, while the pathophysiological significance of ethanol inhibition of INa seems less important.
Habuchi
Y
Y
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan.
Furukawa
T
T
Tanaka
H
H
Lu
L L
LL
Morikawa
J
J
Yoshimura
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015222:Sodium Channels; D000431:Ethanol