Regulation of a non-selective cation channel of cultured porcine coronary artery smooth muscle cells by tyrosine kinase.

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.