MODULATION OF CA2-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 Ca2+-activated K+ channel activities in freshl y isolated single vascular smooth muscle cells from the rat tail arter y were studied by patch clamp recording technique. Genistein (5-50 mu M) and lavendustin A (10 mu M) increased whole-cell Ca2+-activated Kchannel currents. Increase in single channel activities by genistein a nd lavendustin A was also observed in excised inside-out patches. Diad zein (15 mu M), an inactive analogue of genistein, did not alter chann el activities. Tyrphostin A25 (10 nM), which had no significant effect on whole-cell currents in concentrations up to 50 mu M, increased the open probability of the channels by 841% in inside-out patches. No po tentiation of whole-cell and single channel activities by genistein wa s observed when ATP was omitted from the intracellular solutions. Thes e observations suggest that tyrosine kinase modulates Ca2+-activated K + channel activities in vascular smooth muscle cells.