Effects of genistein on intracellular free-calcium concentration in guinea pig ventricular myocytes.
The effects of genistein (GST) on intracellular calcium concentration ([Ca(2+)](i)) were investigated in guinea pig ventricular myocytes. [Ca(2+)](i) was detected by confocal microscopy and represented by relative fluorescent intensity (FI-F(0)) /FI(0), %). The results showed that GST (10-40 micromol/L) reduced [Ca(2+)](i) in normal Tyrode's solution, Ca(2+)-free Tyrode's solution and normal Tyrode's solution containing 3 mmol/L EGTA in a concentration-dependent manner. The effects of GST on [Ca(2+)](i) in normal Tyrode's solution were partially inhibited by pretreatment with sodium orthovanadate, a potent inhibitor of protein tyrosine phosphatase, or L-type Ca(2+) channel agonist Bay K8644. GST also markedly inhibited the ryanodine-induced [Ca(2+)](i) responses in Ca(2+)-free Tyrode's solution. When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, GST (40 micromol/L) could block the propagating waves of elevated [Ca(2+)](i), and reduce the velocity and duration of propagating waves. These results suggest that GST may reduce the [Ca(2+)](i) in isolated guinea pig ventricular myocytes. The inhibition of voltage-dependent Ca(2+) channel, tyrosine kinase inhibition, and alleviation of Ca(2+) release from SR are possibly involved in the GST effect.
Ji
En-Sheng
ES
Departments of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Wang
Chuan
C
He
Rui-Rong
RR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type; D019833:Genistein / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles; D008297:Male; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D014638:Vanadates; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019833:Genistein; D017027:Protein Tyrosine Phosphatases; D002118:Calcium