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 similar to 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 mu M 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. (C) 2000 Elsevier Science B.V. All rights reserved.