Activation of voltage-dependent calcium channels in Kupffer cells by chronic treatment with alcohol in the rat.

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.