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 recent ly reported that Kupffer cells contain L-type voltage-dependent Ca++ c hannels. The purpose of the present study was to evaluate the effect o f chronic ethanol treatment on Ca++ channels. Kupffer cells were isola ted from rats fed either a control liquid diet or a liquid ethanol-con taining diet for 5 to 8 weeks. The cytosolic free calcium concentratio n ([Ca++]i) was measured in freshly isolated Kupffer cells with the fl uorescent Ca++ indicator, fura-2. In Kupffer cells isolated from the c ontrol 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 con centration-response curve for K+ was shifted significantly (P < .01) t o the left in cells isolated from ethanol-treated rats (half-maximal e ffect, 73 +/- 1 mM K+). When extracellular Ca++ was omitted from the i ncubation medium or the dihydropyridine-type calcium channel blocker n itrendipine (10 muM) was added, the increase in [Ca++]i caused by depo larization was prevented completely. Thus, these data indicate that ch ronic ethanol treatment in vivo makes L-type voltage-dependent Ca++ ch annels in Kupffer cells easier to open, a phenomenon that could be inv olved in the mechanism of alcoholic liver injury.