三羟异黄酮对豚鼠心室肌细胞L-型钙通道电流的影响(英文)  

Effect of genistein on L-type calcium current in guinea pig ventricular myocytes

作　　者：吉恩生[1] 尹京湘[1] 马会杰[1] 何瑞荣[1] 

机构地区：[1]河北医科大学基础医学研究所生理室,石家庄050017

出　　处：《生理学报》2004年第4期466-470,共5页Acta Physiologica Sinica

摘　　要：本实验用全细胞膜片钳技术观察三羟异黄酮(genistein,GST)对豚鼠心室肌细胞L-钙通道电流(ICa、L)的影响。结果如下:(1)GST(10、50、100 μmol/L)可浓度依赖性地降低ICa,L(n=6,P<0.01)。GST的非活性结构类似物daidzein(100μmol/L),在同一浓度范围对ICa,L没有影响(n=5,P>0.05)。(2)GST使I-V曲线上移,但对ICa,L的电压依赖特征和最大激活电压无明显影响。(3)GST对ICa,L的激活动力学特性也无影响,但可使钙电流稳态失活曲线左移。V0.5从对照的-28.6±0.6 mV变为-32.8±1.1mV,κ值从对照的5.8±0.5 mV升至6.5±0.9 mV(n=6,P<0.05)。(4)GST明显使复活曲线右移,从而使ICa,L从失活状态下恢复明显减慢(n=7,P<0.01)。(5)酪氨酸磷酸酶抑制剂正钒酸钠(1 mmol/L)显著对抗GST引起的ICa,L抑制效应(n=6,P<0.01)。根据以上结果得出的结论是:GST抑制ICa,L加速钙通道失活和钙通道在失活状态下恢复减慢;GST对ICa,L的这种抑制作用与蛋白酪氨酸激酶(PTK)抑制有关。This paper was aimed to study the effect of genistein (GST) on L-type calcium current (ICa,L) in isolated guinea pig ventricular myocytes using whole cell patch-clamp recording technique. The results are as follows. (1) GST (10, 50, 100 μmol/L) reduced the voltage-activated peak amplitude of ICa,L in a concentration-dependent manner. Daidzein (100μmol/L), a structural analogue of GST which has little or no inhibitory effect on tyrosine kinase, produced no effect over the same concentration range on ICa,L(n=5, P>0.05). (2) GST up- shifted the current-voltage (I-V) curve, but the characteristics of I-V relationship were not significantly altered, and the maximal activation voltage of ICa,L was not different from that of control. GST did not affect the activation kinetics of ICa,L (3) GST markedly shifted the steady-state inactivation curve of ICa,L to the left, and accelerated the voltage-dependent steady-state inactivation of ICa,L V0.5 value was -28.6±0.6 mV in the control and -32.8±1.1 mV in the presence of GST. The κvalues were 5.8±0.5 mV and 6.5±0.9 mV, respectively (n=6, P<0.05). (4) GST markedly shifted the curve of time-dependent recovery of ICa,L from the steady-state inactivation to the right, and slowed down the recovery of ICa,L from inactivation (n=7, P<0.01). (5) Sodium orthovanadate (1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited GST-induced inhibition (n=6, P<0.01). From the results obtained it is concluded that genistein inhibits ICa,L and acts on the inactivated state of L-type calcium channel. This inhibitory effect of GST involves protein tyrosine kinase inhibition in guinea pig ventricular myocytes.

关 键 词：三羟异黄酮 膜片箝技术 心肌 L-型钙通道 

分 类 号：R285[医药卫生—中药学]