Two different types of channels are targets for potassium channel openers in Xenopus oocytes.
K+ channel openers elicit K+ currents in follicle-enclosed Xenopus oocytes. The most potent activators are the pinacidil derivatives P1075 and P1060. The rank order of potency to activate K+ currents in follicle-enclosed oocytes was: P1075 (K0.5:5 microM) greater than P1060 (K0.5:12 microM) greater than BRL38227 (lemakalim) (K0.5:77 microM) greater than RP61410 (K0.5:100 microM) greater than (-)pinacidil (K0.5:300 microM). Minoxidil sulfate, nicorandil, RP49356 and diazoxide were ineffective. Activation by the K+ channel openers could be abolished by the antidiabetic sulfonylurea glibenclamide. It was not affected by the blocker of the Ca(2+)-activated K+ channels charybdotoxin. The various K+ channel openers failed to activate glibenclamide-sensitive K+ channels in defolliculated oocytes, but BRL derivatives (K0.5 for BRL38226 is 150 microM) and RP61419 inhibited a background current. The channel responsible for this background current is K+ permeable but not fully selective for K+. It is resistant to glibenclamide. It is inhibited by Ba2+, 4-aminopyridine, Co2+, Ni2+ and La3+.
Honoré
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Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Valbonne, France.
Lazdunski
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D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004553:Electric Conductivity; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology*; D009930:Organic Chemicals; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014982:Xenopus laevis
D001578:Benzopyrans; D006146:Guanidines; D009930:Organic Chemicals; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C070565:RP 61419; C058754:N'-cyano-N-(3-pyridyl)-N''-(t-butyl)guanidine; D020110:Pinacidil; D005905:Glyburide