Morales J A, Ram J L, Song J, Brown R A
Department of Physiology, Wayne State University, Detroit, Michigan 48201, USA.
Toxicol Appl Pharmacol. 1997 Mar;143(1):70-4. doi: 10.1006/taap.1996.8072.
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.
乙醇摄入往往伴随着心脏和血管功能障碍的增加。潜在机制可能包括乙醇代谢的主要副产物乙醛（ACA）的直接作用，此前已表明乙醛可降低氯化钾和去甲肾上腺素引起的离体主动脉环收缩。为了确定ACA是否通过直接作用于血管平滑肌细胞的肌膜钙电流来降低血管收缩性，使用全细胞膜片钳技术研究了主动脉平滑肌细胞系（A7r5）中的钙通道电流。以钡离子作为主要电荷载体，电极中含有钙离子，并使用四乙铵阻断钾电流，斜坡去极化激活了主要由L型钙通道电流组成的内向电流。ACA导致内向电流逐渐下降，在4分钟内30 mM ACA使内向电流显著降低21.2±4.3%（n = 6个细胞；p < 0.01），8分钟内降低39.4±6.8%（n = 5个细胞，p < 0.001）。虽然10 mM ACA在4分钟时内向电流的下降不显著，但在8分钟（15.5±3.5%，n = 9个细胞）和12分钟（25.2±6.7%，n = 3个细胞）时10 mM ACA有显著（p < 0.05）降低。响应ACA时电流的电压依赖性没有明显变化。本研究结果支持以下假设：ACA抑制钾引起的收缩的潜在原因之一是抑制平滑肌细胞中电压依赖性钙电流。
