酒精和局部麻醉剂对脑突触膜囊泡中钠依赖性钙通量的影响。

Alcohol and local anesthetic effects on Na+-dependent Ca2+ fluxes in brain synaptic membrane vesicles.

作者信息

Michaelis M L, Michaelis E K

出版信息

Biochem Pharmacol. 1983 Mar 15;32(6):963-9. doi: 10.1016/0006-2952(83)90612-3.

Abstract

Resealed synaptic plasma membrane vesicles exhibit Na+-dependent Ca2+ transport activity which may participate in regulation of free Ca2+ concentrations in nerve endings. Sodium chloride-loaded vesicles took up Ca2+ from the external medium (150 mM KCl-25 mM Tris/HCl) in the presence of an outward-directed Na+ gradient, a Ca2+ concentration of 38.6 microM producing half-maximal uptake at 23 degrees. Methanol (5-200 mM) and low concentrations of ethanol (5-25 mM) enhanced the Na+-dependent Ca2+ influx measured at 23 degrees. Higher ethanol concentrations (100-600 mM), as well as 1-propanol and 1-butanol (10-200 mM), produced only inhibition of Ca2+ fluxes. Dixon plot analysis of the inhibitory phase revealed that ethanol inhibited Ca2+ uptake in an apparently competitive manner with respect to Ca2+ concentration, and the Ki obtained from these experiments was 1.01 M ethanol. The inhibition of Ca2+ fluxes by butanol was non-competitive, and the Ki was 68.6 mM. The local anesthetics dibucaine and tetracaine also inhibited Ca2+ fluxes with IC50 values of 1.8 mM for tetracaine and 0.46 mM for dibucaine. The possible physiologic consequences of this inhibition of Na+-Ca2+ countertransport is synaptic membranes by the alcohols and local anesthetics are discussed with regard to neuronal transmission and membrane conductance.

摘要

重新封闭的突触质膜囊泡表现出钠依赖性钙转运活性，这可能参与神经末梢游离钙浓度的调节。加载氯化钠的囊泡在存在外向钠梯度的情况下，从外部介质（150 mM KCl - 25 mM Tris/HCl）中摄取钙，在23℃时，38.6 microM的钙浓度产生半数最大摄取量。甲醇（5 - 200 mM）和低浓度乙醇（5 - 25 mM）增强了在23℃时测量的钠依赖性钙内流。较高浓度的乙醇（100 - 600 mM）以及1 - 丙醇和1 - 丁醇（10 - 200 mM）仅抑制钙通量。对抑制阶段的迪克森图分析表明，乙醇以明显竞争性的方式抑制钙摄取，相对于钙浓度而言，从这些实验中获得的Ki为1.01 M乙醇。丁醇对钙通量的抑制是非竞争性的，Ki为68.6 mM。局部麻醉药丁卡因和丁哌卡因也抑制钙通量，丁卡因的IC50值为1.8 mM，丁哌卡因为0.46 mM。关于神经元传递和膜电导，讨论了醇类和局部麻醉药对突触膜钠钙逆向转运的这种抑制作用可能产生的生理后果。