title: Regulation of a non-selective cation channel of cultured porcine coronary artery smooth muscle cells by tyrosine kinase.
abstract: A non-selective cation channel was found in primary cultured porcine coronary artery smooth muscle cells. In patch-clamp studies in the cell-attached mode, this channel was activated by bath application of genistein, a specific inhibitor of tyrosine kinase, but not by daidzein, which is similar in structure to genistein but has no inhibitory effect on tyrosine kinase. This channel discriminated poorly between Na+ and K+ (permeability ratio PNa/PK = 1.03), and also transported Ca2+. The single-channel conductance measured with a pipette solution containing 150 mM Na+ was 139 +/- 24 pS (mean +/- SD, n = 5), and that for the inward current measured with 100 mM Ca2+ solution was 25 +/- 9 pS (n = 3). This non-selective cation channel was also activated by staurosporine, a non-specific protein kinase inhibitor, but not by H-7, an inhibitor of protein serine/threonine kinase. These results suggest that the activity of the non-selective cation channel is negatively regulated by tyrosine kinase activity, and thus a decrease of the enzyme activity in porcine coronary artery smooth muscle cells may result in membrane depolarization and Ca2+ entry.
authors.affiliation: Laboratory of Health Chemistry, Faculty of Pharmaceutical Sciences, Tokushima University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Minami
authors.forename: K
authors.initials: K
authors.lastname: Fukuzawa
authors.forename: I
authors.initials: I
authors.lastname: Inoue
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019833:Genistein; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D019311:Staurosporine; D013552:Swine
chemical_list: D000470:Alkaloids; D002412:Cations; D007473:Ion Channels; D007529:Isoflavones; D007546:Isoquinolines; D010879:Piperazines; C004742:daidzein; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine