青藤碱对豚鼠单个心室肌细胞膜钠、钙离子通道的阻滞作用

应用膜片钳全细胞记录技术研究青藤碱 (Sin)对酶解分离的豚鼠单个心室肌细胞膜钠离子电流 (INa)、L型钙电流 (ICa L)的影响。发现 1,5 ,10 μmol/L的Sin分别使INa峰值 (INamax)较用药前下降 2 3.2 %、36 .1%和 6 0 % (n =8,P均 <0 .0 5 ) ;使ICa L峰值 (ICa Lmax)较用药前下降了 12 .8% ,35 .9%和 46 .9% (n =8,P均 <0 .0 1)。Sin使INa及ICa L电流 电压曲线上移 ,但不使其峰值电位偏移。Sin还浓度依赖性减慢钠通道灭活后恢复过程。当刺激频率分别为 0 .5 ,1,2Hz时 ,5 μmol/LSin使INamax较用药前分别下降了 36 .1%、41.5 %和 48.0 % (n =8,P均 <0 .0 1)。结果表明 ,Sin对INa具浓度和频率依赖性阻滞作用 ,可能作用于其失活状态 ;Sin对ICa L具浓度依赖性阻滞作用。这可能为其抗心律失常的重要机制。

The Effect of Sinomenine on Sodium,L type Callium current in Guinea Pig Ventricular Myocytes.

Whole cell patch clamp technique was used to investigate the effect of sinomenine (Sin) on sodium current (I Na ) and L type callium (I Ca L ) in isolated guinea pig ventricular myocytes.Sin at 1,5,10 μmol/L decreased peak I Na (I Namax ) 23.3%,36.1%,60%,respectively ( n =8, P <0.05);and reduced I Ca Lmax 12.8%,35.9% and 46.4%,respectively ( n =8, P <0.01).Sin shifted the I V curve of I Na and I Ca L without change of their peak current potentials.Sin delayed the recovery time course of I Na from inactive state in dose dependant manner.When the stimulation frequency was 0.5,1,2 Hz,Sin at 5 μmol/L reduced I Namax 36.1%,41.5% and 48.0%,respectively ( n =8, P <0.05).It can be concluded that Sin blocks I Na and I Ca L in a concentration dependant manner and probably inhibits I Na in its inactive state,which may contribute to its antiarrhythmic effect.