title: Activation of voltage-dependent calcium channels in Kupffer cells by chronic treatment with alcohol in the rat.
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.
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill.
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: J J
authors.initials: JJ
authors.lastname: Lemasters
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D005260:Female; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009568:Nitrendipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D009568:Nitrendipine; D002118:Calcium