Acetaldehyde inhibits current through voltage-dependent calcium channels.
Ethanol consumption is often accompanied by an increase in both cardiac and vascular dysfunction. Underlying mechanisms may include direct actions of acetaldehyde (ACA), the principal by-product of ethanol metabolism, which has previously been shown to decrease both KCl- and nonrepinephrine-elicited contractions of isolated aortic rings. To determine whether ACA reduces vascular contractility through a direct action on sarcolemmal Ca2+ currents of vascular smooth muscle cells, Ca2+ channel currents in an aortic smooth muscle cell line (A7r5) were studied using the whole-cell patch clamping technique. With Ba2+ as the major charge carrier, Ca+ in the electrode, and TEA to block K+ currents, ramp depolarization activated an inward current consisting mostly of current through L-type Ca2+ channels. ACA caused a progressive decline in inward current, causing a significant reduction in 30 mM ACA of 21.2 +/- 4.3% (n = 6 cells; p < 0.01) within 4 min and 39.4 +/- 6.8% (n = 5 cells, p < 0.001) reduction within 8 min. Although the decline in inward current in 10 mM ACA was not significant at 4 min, significant (p < 0.05) reductions in 10 mM ACA were present at 8 min (15.5 +/- 3.5%, n = 9 cells) and 12 min (25.2 +/- 6.7%, n = 3 cells). There was no apparent shift in the voltage dependence of the current in response to ACA. The results of this study support the hypothesis that one of the underlying causes of ACA inhibition of potassium-elicited contraction is inhibition of voltage-dependent Ca2+ currents in smooth muscle cells.
Morales
J A
JA
Department of Physiology, Wayne State University, Detroit, Michigan 48201, USA.
Ram
J L
JL
Song
J
J
Brown
R A
RA
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004553:Electric Conductivity; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D014664:Vasodilation / Q000187:drug effects*
D015220:Calcium Channels; D000079:Acetaldehyde; D002118:Calcium