Genistein directly inhibits L-type calcium currents but potentiates cAMP-dependent chloride currents in cardiomyocytes.
We have examined the possible modulatory effects of genistein, a specific tyrosine kinase inhibitor, on cardiac L-type calcium currents and cAMP-dependent chloride currents in guinea pig ventricular myocytes. With one-suction electrode voltage-clamp technique, genistein dose-dependently and reversibly inhibited L-type calcium currents in cardiomyocytes (Km = 17.5 microM). Neither threshold potential nor the peak potential of current-voltage relationship was affected. Interestingly, daidzein (an inactive analogue of genistein) also depressed L-type calcium currents. When L-type calcium currents were directly activated by Bay K 8644, genistein was able to exert an inhibitory action. In contrast, genistein potentiated cardiac cAMP-dependent chloride currents activated by either isoproterenol or 3-isobutyl-1-methylxanthine. These results suggest that genistein may directly inhibit L-type calcium currents but may potentiate cAMP-dependent chloride currents in the heart.
Chiang
C E
CE
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
Chen
S A
SA
Chang
M S
MS
Lin
C I
CI
Luk
H N
HN
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D019833:Genistein; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D007529:Isoflavones; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019833:Genistein; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine