Barchfeld G L, Deamer D W
Department of Animal Physiology, University of California, Davis 95616.
Biochim Biophys Acta. 1988 Sep 15;944(1):40-8. doi: 10.1016/0005-2736(88)90314-8.
Past work has shown that general anesthetics perturb the membranes of isolated synaptic vesicles, thereby increasing permeability to protons and inhibiting the ability of the vesicles to take up catecholamines. It has been proposed that such effects may produce anesthesia through inhibition of synaptic transmission. The mechanisms of perturbation is unknown. Two possible explanations include alterations of dielectric constant or production of defects as anesthetics partition into the bilayer phase. In order to choose between these alternatives, we measured the effect of nine alcohols and two alkanes on liposome permeability to protons and potassium. Ionic permeability was increased by alcohols and alkanes to similar degrees, thereby ruling out direct effects on the membrane dielectric constant caused by partitioning of anesthetics into the bilayer. Other experiments confirmed earlier reports that the enhanced permeability caused by anesthetics is not specific for protons. We conclude that these membrane perturbants act by increasing the number of transient, ion-conducting defects normally present in the bilayer structure.
过去的研究表明,全身麻醉药会扰乱分离出的突触小泡的膜,从而增加对质子的通透性,并抑制小泡摄取儿茶酚胺的能力。有人提出,这种效应可能通过抑制突触传递而产生麻醉作用。其扰动机制尚不清楚。两种可能的解释包括介电常数的改变或麻醉药分配到双层相中时产生缺陷。为了在这些选择中做出决定,我们测量了九种醇类和两种烷烃对脂质体对质子和钾离子通透性的影响。醇类和烷烃使离子通透性增加的程度相似,从而排除了麻醉药分配到双层中对膜介电常数的直接影响。其他实验证实了早期的报道,即麻醉药引起的通透性增强并非质子特异性的。我们得出结论,这些膜扰动剂的作用是增加双层结构中正常存在的瞬时离子传导缺陷的数量。