Genistein inhibits the inward rectifying potassium current in guinea pig ventricular myocytes.
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.
Chiang
Chern-En
CE
Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. cechiang@vghtpe.gov.tw
Luk
Hsiang-Ning
HN
Chen
Ling-Lan
LL
Wang
Tsui-Min
TM
Ding
Philip Yu-An
PY
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
D007529:Isoflavones; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D020032:Tyrphostins; C118515:tyrphostin 51; C004742:daidzein; D019833:Genistein; D011505:Protein-Tyrosine Kinases