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.
Xiong
Z
Z
University of Ottawa Heart Institute, Canada.
Burnette
E
E
Cheung
D W
DW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D020032:Tyrphostins
D004791:Enzyme Inhibitors; D007529:Isoflavones; D009570:Nitriles; D010636:Phenols; D015221:Potassium Channels; D020032:Tyrphostins; C079836:tyrphostin 25; C062898:lavendustin A; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium