Modulation of Ca2+-activated K+ channel activity by tyrosine kinase inhibitors in vascular smooth muscle cell

Abstract

The effects of the tyrosine kinase inhibitors genistein, lavendustin A, and tyrphostin A25 on Ca²⁺-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 μM) and lavendustin A (10 μM) increased whole-cell Ca²⁺-activated K⁺ channel currents. Increase in single channel activities by genistein and lavendustin A was also observed in excised inside-out patches. Diadzein (15 μM), 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 μM, 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 Ca²⁺-activated K⁺ channel activities in vascular smooth muscle cells.