Inhibition of Ca2+-activated K+ channels in pig pancreatic acinar cells by Ba2+, Ca2+, quinine and quinidine.
Patch-clamp whole-cell and single-channel current recordings were made from pig pancreatic acinar cells to test the effects of quinine, quinidine, Ba2+ and Ca2+. Voltage-clamp current recordings from single isolated cells showed that high external concentrations of Ba2+ or Ca2+ (88 mM) abolished the outward K+ currents normally associated with depolarizing voltage steps. Lower concentrations of Ca2+ only had small inhibitory effects whereas 11 mM Ba2+ almost blocked the K+ current. 5.5 mM Ba2+ reduced the outward K+ current to less than 30% of the control value. Both external quinine and quinidine (200-500 microM) markedly reduced whole-cell outward K+ currents. In single-channel current studies it was shown that external Ba2+ (1-5 mM) markedly reduced the probability of opening of high-conductance Ca2+ and voltage-activated K+ channels whereas internal Ba2+ (6 X 10(-6) to 3 X 10(-5) M) caused activation at negative membrane potentials and inhibition at positive potentials. Quinidine (200-400 microM) evoked rapid chopping of single K+ channel openings acting both from the outside and inside of the membrane and in this way markedly reduced the total current passing through the channels.
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N
Iwatsuki
O H
OH
Petersen
D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D010179:Pancreas / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D013552:Swine
D007473:Ion Channels; D001464:Barium; D011803:Quinine; D011802:Quinidine; D011188:Potassium; D002118:Calcium