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应用膜片钳全细胞记录技术,观察了具有正性肌力作用的苄基异喹啉衍化物IQ23,即1-〔对甲氧苄基-2-(N-苄基,N-甲基)〕-6,7-二甲氧基异喹啉盐酸盐,对豚鼠心室肌分离细胞的Ca2+通道,以及CHOH10细胞表达的Ca2+通道α1亚单位的作用.结果显示,当豚鼠心室肌细胞从保持电位(Vh)-50mV除极至测试电位(Vt)0mV时,IQ233,10μmol·L-1分别使Ca2+电流(ICa)由对照的(0.47±0.23)nA增至(0.57±0.23)和(0.79±0.31)nA(P<0.05).在CHOH10细胞Vt为20mV时,IQ2310μmol·L-1电压依赖性的增强Ba2+电流(IBa),IBa从(0.45±0.10)nA增至(0.67±0.20)nA(Vh=-80mV),或从(0.43±0.08)nA增至(0.60±0.14)nA(Vh=-40mV).IQ2310和30μmol·L-1还分别使电流-电压曲线的峰值和失活曲线的半失活电位向负膜电位方向移动.实验结果表明,IQ23通过作用于通道的α1亚单位,对心肌L型Ca2+通道产生电压依赖性激动作用,此作用为其正性肌力效应提供了部分解释.
Patch clamp whole cell recording technique was used to observe the positive inotropic effect of benzylisoquinoline derivative IQ23, namely 1- [p-methoxybenzyl-2- (N-benzyl, N-methyl) ] -6,7-dimethoxyisoquinoline hydrochloride on the Ca2 + channel of guinea pig ventricular myocytes and the Ca2 + channel α1 subunit of CHOH10 cells. The results showed that when the guinea pig ventricular myocytes were depolarized from the holding potential (Vh) -50mV to the test potential (Vt) at 0mV, IQ233,10μmol·L-1 decreased the Ca2 + current (ICa) from 0.47 ± 0 .23) nA increased to (0.57 ± 0.23) and (0.79 ± 0.31) nA (P <0.05). When the Vt of CHOH10 cells was 20mV, IQ2310μmol·L-1 increased voltage-dependently the Ba2 + current (IBa) and IBa increased from (0.45 ± 0.10) nA to (0.67 ± 0.20) nA = -80 mV) or from (0.43 ± 0.08) nA to (0.60 ± 0.14) nA (Vh = -40 mV). IQ2310 and 30 μmol·L-1 also shifted the peak of the current-voltage curve and the inactivation potential of the inactivation curve to the negative membrane potential, respectively. The experimental results show that IQ23 exerts a voltage-dependent agonistic effect on the L-type Ca2 + channel of myocardium by acting on the α1 subunit of the channel, and this effect provides a partial explanation for its positive inotropic effect.