Glibenclamide-sensitive K+ channels underlying levcromakalim-induced relaxation in pig urethra.
To investigate the possible mechanisms involved in the stable and long-lasting levcromakalim-induced relaxation of the resting urethral tone, we have performed mechanical and voltage-clamp experiments using intact tissue and isolated cells from pig urethra, respectively. At negative membrane potentials, levcromakalim induced time- and voltage-independent membrane currents in whole-cell configurations. In cell-attached patches, levcromakalim not only increased the open-state probability (the NP(0) value) of the glibenclamide-sensitive 43 pS K+ channel (K(GS)) in a concentration-dependent manner, but also activated K(GS) with a time- and voltage-independence. During long burst-like channel activity, neither the mean open lifetime nor the mean closed time of K(GS) exhibited voltage-dependency between -100 and - 40 mV. It is concluded that levcromakalim causes a stable and potent relaxation of pig urethra through opening of K(GS) which possesses time- and voltage-independent activating mechanisms.
Teramoto
N
N
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Brading
A F
AF
Ito
Y
Y
D000818:Animals; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009126:Muscle Relaxation / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D013552:Swine; D013997:Time Factors; D014521:Urethra / Q000187:drug effects*