Blocking actions of glibenclamide on ATP-sensitive K+ channels in pig urethral myocytes.
The inhibitory effects of glibenclamide on the levcromakalim-induced ATP-sensitive K+ (K(ATP)) channels were investigated with cell-attached configuration in pig proximal urethra. Application of 10 microM glibenclamide reversibly inhibited the activity of the 100 microM levcromakalim-induced K(ATP) channel, decreasing not only the channel open probability but also the amplitude of unitary current. The inhibitory concentration-response curve of the glibenclamide-induced sublevel conductance of K(ATP) channel was shifted to the right (IC50 = 4.7 microM), compared with the levcromakalim-induced K(ATP) channel (full conductance, IC50 = 0.5 microM). Glibenclamide is the first reported sulphonylurea to selectively block K(ATP) channel, not only by decreasing the channel activity but also by reducing the unitary amplitude in smooth muscle.
Teramoto
Noriyoshi
N
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. noritera@linne.med.kyushu-u.ac.jp
Zhu
Hai-Lei
HL
Ito
Yushi
Y
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000465:Algorithms; D000818:Animals; D019806:Cromakalim / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects; D064233:Sulfonylurea Receptors; D013552:Swine; D014521:Urethra / Q000166:cytology*
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D019806:Cromakalim; D005905:Glyburide