Mongo K G, Vassort G
Laboratoire Physiologie Cellulaire, U-241 INSERM, Université Paris-Sud, Orsay, France.
J Mol Cell Cardiol. 1990 Sep;22(9):939-53. doi: 10.1016/0022-2828(90)91034-5.
Changes in the Ca current, ICa, evoked by ethanol, long chain alcohols (hexanol, octanol and dodecanol) and two halogenated anesthetics (chloroform and halothane) were studied in single isolated frog ventricular cells using the whole cell patch clamp technique. Each of these general anesthetics induced a concentration-dependent decrease in ICa which was usually followed by a partial recovery during long application (5 min). However, an increase in ICa was observed with low ethanol concentrations. The potency of the alcohols was related to their oil-water partition coefficient in that the longer the carbon chain the greater the reduction in ICa. For example, to reduce ICa to half its control amplitude required 300 mM ethanol but only 0.3 microns dodecanol. The kinetics of ICa were also altered by exposure to the alcohols. The halogenated derivatives also decreased ICa and altered the kinetics of ICa, but in a different way to the alcohols. The complex and different alterations of ICa are probably the consequence of multifactorial effects induced by the general anesthetics. Previous suggestions have included alterations in the membrane lipid bilayer, membrane surface charge and hydrophobic pockets on channel proteins. We suggest that the increase in Cai may also participate to these effects.
采用全细胞膜片钳技术,在单个分离的蛙心室肌细胞中研究了乙醇、长链醇(己醇、辛醇和十二醇)以及两种卤代麻醉剂(氯仿和氟烷)诱发的钙电流(ICa)变化。这些全身麻醉剂中的每一种都能引起ICa浓度依赖性降低,长时间应用(5分钟)后通常会部分恢复。然而,在低乙醇浓度下观察到ICa增加。醇类的效力与其油水分配系数有关,即碳链越长,ICa降低越大。例如,将ICa降低至其对照幅度的一半,需要300 mM乙醇,但仅需0.3 μM十二醇。暴露于醇类也会改变ICa的动力学。卤代衍生物也会降低ICa并改变ICa的动力学,但方式与醇类不同。ICa的复杂且不同的改变可能是全身麻醉剂诱导的多因素效应的结果。先前的推测包括膜脂质双层、膜表面电荷和通道蛋白上的疏水口袋的改变。我们认为细胞内钙(Cai)的增加也可能参与了这些效应。