Cromakalim-induced membrane current in guinea-pig tracheal smooth muscle cells.
The characteristics of the cromakalim-induced membrane current were examined in single tracheal myocytes of the guinea-pig under voltage-clamp conditions. When K(+) concentrations in the pipette and bathing solutions were approximately 140 mM, cromakalim activated a membrane current (I(crom)) which was inward at -60 mV and reversed at -2 mV. I(crom) was blocked by 10 microM glibenclamide and potentiated when the ATP concentration in the pipette solution was decreased. The K(d) and Hill coefficient of glibenclamide for I(crom) block were 200 nM and 1.05, respectively. Application of the tyrosine kinase inhibitors, genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamid (ST638), reduced I(crom) in a concentration-dependent manner. Daidzein, which does not inhibit tyrosine kinase, was about 10 times less effective than genistein. Herbimycin A had no effect on I(crom). Internal application of these inhibitors from the pipette did not affect I(crom). In conclusion, cromakalim is a potent activator of the ATP-sensitive K(+) channel (K(ATP) channel) in guinea-pig tracheal myocytes. The inhibition of I(crom) by genistein and ST638 may be due to the direct block of the channel from outside.
Matsushita
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya, Japan.
Henmi
S
S
Muraki
K
K
Imaizumi
Y
Y
Watanabe
M
M
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*
D001993:Bronchodilator Agents; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D011188:Potassium