Goto M, Lemasters J J, Thurman R G
Department of Pharmacology, University of North Carolina at Chapel Hill.
J Pharmacol Exp Ther. 1993 Dec;267(3):1264-8.
Calcium is essential for activation of Kupffer cells and it was recently reported that Kupffer cells contain L-type voltage-dependent Ca++ channels. The purpose of the present study was to evaluate the effect of chronic ethanol treatment on Ca++ channels. Kupffer cells were isolated from rats fed either a control liquid diet or a liquid ethanol-containing diet for 5 to 8 weeks. The cytosolic free calcium concentration ([Ca++]i) was measured in freshly isolated Kupffer cells with the fluorescent Ca++ indicator, fura-2. In Kupffer cells isolated from the control group, partial replacement of extracellular Na+ by K+ caused a concentration-dependent increase in [Ca++]i (half-maximal effect, 83 +/- 1 mM K+) presumably as a result of membrane depolarization. The concentration-response curve for K+ was shifted significantly (P < .01) to the left in cells isolated from ethanol-treated rats (half-maximal effect, 73 +/- 1 mM K+). When extracellular Ca++ was omitted from the incubation medium or the dihydropyridine-type calcium channel blocker nitrendipine (10 microM) was added, the increase in [Ca++]i caused by depolarization was prevented completely. Thus, these data indicate that chronic ethanol treatment in vivo makes L-type voltage-dependent Ca++ channels in Kupffer cells easier to open, a phenomenon that could be involved in the mechanism of alcoholic liver injury.
钙对于库普弗细胞的激活至关重要，最近有报道称库普弗细胞含有L型电压依赖性钙离子通道。本研究的目的是评估慢性乙醇处理对钙离子通道的影响。从喂食对照液体饮食或含乙醇液体饮食5至8周的大鼠中分离出库普弗细胞。用荧光钙离子指示剂fura-2测量新鲜分离的库普弗细胞中的胞质游离钙浓度（[Ca++]i）。在从对照组分离的库普弗细胞中，用K+部分替代细胞外Na+导致[Ca++]i浓度依赖性增加（半数最大效应，83±1 mM K+），这可能是膜去极化的结果。在从乙醇处理的大鼠分离的细胞中，K+的浓度-反应曲线显著向左移动（P <.01）（半数最大效应，73±1 mM K+）。当孵育培养基中省略细胞外Ca++或加入二氢吡啶型钙通道阻滞剂尼群地平（10 microM）时，去极化引起的[Ca++]i增加被完全阻止。因此，这些数据表明体内慢性乙醇处理使库普弗细胞中的L型电压依赖性钙离子通道更容易打开，这一现象可能与酒精性肝损伤的机制有关。
