Modulation of Ca(2+)-activated K+ channel activity by tyrosine kinase inhibitors in vascular smooth muscle cell.

The effects of the tyrosine kinase inhibitors genistein, lavendustin A, and tyrphostin A25 on Ca(2+)-activated K+ channel activities in freshly isolated single vascular smooth muscle cells from the rat tail artery were studied by patch clamp recording technique. Genistein (5-50 microM) and lavendustin A (10 microM) increased whole-cell Ca(2+)-activated K+ channel currents. Increase in single channel activities by genistein and lavendustin A was also observed in excised inside-out patches. Diadzein (15 microM), an inactive analogue of genistein, did not alter channel activities. Tyrphostin A25 (10 nM), which had no significant effect on whole-cell currents in concentrations up to 50 microM, increased the open probability of the channels by 841% in inside-out patches. No potentiation of whole-cell and single channel activities by genistein was observed when ATP was omitted from the intracellular solutions. These observations suggest that tyrosine kinase modulates Ca(2+)-activated K+ channel activities in vascular smooth muscle cells.