Ethanol inhibits electrically-induced calcium transients in isolated rat cardiac myocytes.
The fluorescent Ca2+ indicator fura-2 was used to follow cytosolic Ca2+ transients during excitation-contraction coupling in suspensions of isolated rat heart cells induced to beat synchronously by electrical field stimulation. The Ca2+ transient reached a maximum at about 30 ms after application of the electrical stimulus and then relaxed to the basal level over the following 200 ms. Treatment of the myocytes with 0.25 to 2.0% ethanol (40 to 340 mM) caused a decrease in the peak of the Ca2+ transient, with no apparent change in the time to peak. This effect of ethanol occurred progressively over a period of about 1 min before a new stable state was achieved. At 1% ethanol the peak Ca2+ level was reduced by 50%. Ethanol reversed the stimulatory effect of isoproterenol on peak Ca2+ and at high levels of ethanol the beta-adrenergic agonist no longer caused any enhancement of the Ca2+ transient. Ethanol did not cause any marked change in the basal Ca2+ level between beats. The effects of ethanol were readily reversible. These results suggest that the negative inotropic effect of ethanol observed in intact cardiac muscle preparations may result in part from interference with the Ca2+ fluxes responsible for excitation-contraction coupling in ventricular myocytes.
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.
A P
AP
Thomas
E J
EJ
Sass
T T
TT
Tun-Kirchmann
E
E
Rubin
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001572:Benzofurans; D005456:Fluorescent Dyes; D000431:Ethanol; D007545:Isoproterenol; D002118:Calcium; D016257:Fura-2