Protein tyrosine kinase-dependent modulation of voltage-dependent potassium channels by genistein in rat cardiac ventricular myocytes

Abstract

Effects of the isoflavone protein tyrosine kinase (PTK) inhibitor genistein on voltage-dependent K + currents, i.e., transient outward K + current ( I to), sustained K + current ( I ss), and inward rectifier K + current ( I K1) were studied in rat cardiac ventricular myocytes. It was found that I to was reversibly inhibited by genistein in a concentration-dependent manner (IC 50=28.1 μM), while I ss was suppressed by genistein with IC 50 of 18.5 μM. In addition, I K1 (at −50 mV) was significantly decreased by 36.3±4.4% with 25 μM genistein. The inhibition of I to, I ss, and I K1 by genistein was significantly reversed by the application of the protein tyrosine phosphatase inhibitor sodium orthovanadate (1 mM). However, I to, I ss, and I K1 were not affected by the non-isoflavone PTK inhibitor tyrphostin A23 (100 μM) and PP2 (1 μM). These results indicate that activation of I to, I ss, and I K1 channels is modulated by genistein-sensitive PTKs in rat ventricular myocytes.