Ionic currents and inhibitory effects of glibenclamide in seminal vesicle smooth muscle cells.
1. Whole-cell voltage-clamp recordings were made from smooth muscle cells isolated from guinea-pig seminal vesicle. 2. When the recording pipette solution contained 130 mM KCl and a low concentration of EGTA (0.2 mM), a dominant outward current was elicited by depolarization to positive of -30 mV from a holding potential of -50 mV. The current was non-inactivating, stimulated by intracellular Ca2+ and blocked by bath-applied 1 mM tetraethylammonium but not 1 mM 3,4 diaminopyridine. 3. If 10 mM EGTA was added to the KCl pipette solution and the holding potential was -50 mV, or more negative, the major current elicited by depolarization to positive of -30 mV was an A-type K(+)-current. This current inactivated rapidly (within 100 ms) and was blocked by bath-applied 1 mM 3,4-diaminopyridine but not 10 mM tetraethylammonium. 4. An inward voltage-gated Ca channel current was observed on depolarization to positive of -30 mV with 1.5 mM Ca2+ or 10 mM Ba2+ in the bath solution and when Ca+ replaced K+ in the pipette. The Ba(2+)-current was shown to be abolished by bath-applied 100 microM Cd2+ and inhibited by 90% by 1 microM nifedipine, and thus appeared to be carried by L-type Ca channels. 5. High concentrations of glibenclamide (10-500 microM) inhibited A-type K(+)-current, Ba(2+)-current and contraction of the whole tissue induced by noradrenaline or electrical field stimulation. 6. From these data we suggest that seminal vesicle smooth muscle cells express Ca2+ -dependent K channels, A-type K channels and L-type Ca channels which are inhibited by tetraethylammonium,3,4-diaminopyridine and nifedipine, respectively. In addition, an unexpected relaxant effect of high concentrations of glibenclamide may be explained by inhibition of the Ca channels.
Sadraei
H
H
Department of Pharmacology, University of Leeds.
Beech
D J
DJ
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001464:Barium / Q000378:metabolism; D001693:Biological Transport, Active; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D012669:Seminal Vesicles / Q000166:cytology / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015220:Calcium Channels; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D001464:Barium; D004533:Egtazic Acid; D019789:Tetraethylammonium; D011189:Potassium Chloride; D015761:4-Aminopyridine; D000077770:Amifampridine; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D009638:Norepinephrine