title: Genistein inhibits the inward rectifying potassium current in guinea pig ventricular myocytes.
abstract: Genistein is an isoflavone with potent inhibitory activity on protein tyrosine kinase. Previous studies have shown that genistein has additional effects, among which the direct blocking effects on various ionic channels have recently been disclosed. Using whole-cell voltage clamp and current clamp techniques, we demonstrate that micromolar concentrations of genistein dose-dependently and reversibly inhibit the inward rectifying K(+) current, and depolarize the resting membrane potential, resulting in abnormal automaticity in guinea pig ventricular myocytes. Interestingly, another potent tyrosine kinase inhibitor, tyrphostin 51, did not produce the same inhibitory effect, while the inactive analogue of genistein, daidzein, had a similar blocking effect. We suggest that genistein directly blocks the inward rectifying K(+) current in ventricular myocytes, and one should be cautious of its pro-arrhythmic effect in clinical use.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. cechiang@vghtpe.gov.tw
authors.forename: Chern-En
authors.initials: CE
authors.lastname: Chiang
authors.forename: Hsiang-Ning
authors.initials: HN
authors.lastname: Luk
authors.forename: Ling-Lan
authors.initials: LL
authors.lastname: Chen
authors.forename: Tsui-Min
authors.initials: TM
authors.lastname: Wang
authors.forename: Philip Yu-An
authors.initials: PY
authors.lastname: Ding
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006168:Guinea Pigs; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D007529:Isoflavones; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D020032:Tyrphostins; C118515:tyrphostin 51; C004742:daidzein; D019833:Genistein; D011505:Protein-Tyrosine Kinases