title: Ethanol activates maxi Ca2+-activated K+ channels of clonal pituitary (GH3) cells.
abstract: The effect of ethanol on maxi Ca2+-activated K+ channels (BK channels) in GH3 pituitary tumor cells was investigated using single-channel recordings and focusing on intracellular signal transduction. In outside-out patches, ethanol caused a transient concentration-dependent increase of BK-channel activity. 30 mm (1.4 per thousand) ethanol significantly increased mean channel open time and channel open probability by 26.3 +/- 9% and 78.8 +/- 10%, respectively; single-channel current amplitude was not affected by ethanol. The augmenting effect of ethanol was blocked in the presence of protein kinase C (PKC) inhibitors staurosporine, bisindolylmaleimide, and PKC (19-31) pseudosubstrate inhibitor as well as by AMP-PNP (5'-adenylylimidodiphosphate), a nonhydrolyzable ATP-analogue, but not by the phospholipase C blocker U-73122. Phosphatase inhibitors microcystin-LR and okadaic acid promoted the ethanol effect. The blocking effect was released at higher concentrations of ethanol (100 mm) suggesting a second site of action or a competition between blockers and ethanol. Our results suggest that the effect of ethanol on BK-channels is mediated by PKC stimulation and phosphorylation of the channels which increases channel activity and hence may influence action potentials duration and hormone secretion.
authors.affiliation: Department of Physiology, Institute of Zoology, University of Salzburg, Hellbrunnerstr. 34, A-5020 Salzburg, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Jakab
authors.forename: T M
authors.initials: TM
authors.lastname: Weiger
authors.forename: A
authors.initials: A
authors.lastname: Hermann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002999:Clone Cells; D000431:Ethanol / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D010902:Pituitary Gland / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D015221:Potassium Channels; D000431:Ethanol; D002118:Calcium