title: 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 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.
authors.affiliation: Institute of Cardiovascular Science and Medicine, University of Hong Kong, SAR Hong Kong, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Gao
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
authors.forename: Tak-Ming
authors.initials: TM
authors.lastname: Wong
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D024642:Potassium Channels, Voltage-Gated; D014638:Vanadates; D019833:Genistein; D011505:Protein-Tyrosine Kinases