Protein tyrosine kinase-dependent modulation of voltage-dependent potassium channels by genistein in rat cardiac ventricular myocytes.
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 microM), while I(ss) was suppressed by genistein with IC(50) of 18.5 microM. In addition, I(K1) (at -50 mV) was significantly decreased by 36.3+/-4.4% with 25 microM 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 microM) and PP2 (1 microM). These results indicate that activation of I(to), I(ss), and I(K1) channels is modulated by genistein-sensitive PTKs in rat ventricular myocytes.
Gao
Zhan
Z
Institute of Cardiovascular Science and Medicine, University of Hong Kong, SAR Hong Kong, China.
Lau
Chu-Pak
CP
Wong
Tak-Ming
TM
Li
Gui-Rong
GR
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D032383:Myocytes, Cardiac / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D024642:Potassium Channels, Voltage-Gated; D014638:Vanadates; D019833:Genistein; D011505:Protein-Tyrosine Kinases