Abstract

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.