Harris N C, Webb C, Greenfield S A
University Department of Pharmacology, Oxford, U.K.
Neuroscience. 1989;31(2):363-70. doi: 10.1016/0306-4522(89)90380-1.
The effects of gamma-hydroxybutyrate have been studied on the membrane properties of pars compacta neurons within the guinea-pig substantia nigra maintained in vitro. The effects of gamma-hydroxybutyrate are to (i) lower input resistance, (ii) hyperpolarize the cell membrane in a dose-dependent manner and (iii) facilitate calcium conductances. These effects are resistant to the blockade of sodium channels with tetrodotoxin and blockade of potassium channels with tetraethylammonium or 4-aminopyridine. Furthermore, these effects are only partially blocked by high doses of the GABA receptor antagonist bicuculline: indeed the effects of the GABA receptor agonist muscimol can be differentiated from those of gamma-hydroxybutyrate in that the latter is sensitive to application of barium ions. The results suggest that gamma-hydroxybutyrate acts to increase utilization of calcium, which in turn leads to an initiation of calcium-dependent events. The functional consequences of these effects of gamma-hydroxybutyrate are discussed with regard to its possible endogenous modulatory actions.
已对γ-羟基丁酸酯对体外培养的豚鼠黑质致密部神经元膜特性的影响进行了研究。γ-羟基丁酸酯的作用包括:(i)降低输入电阻;(ii)以剂量依赖的方式使细胞膜超极化;(iii)促进钙电导。这些作用不受河豚毒素对钠通道的阻断以及四乙铵或4-氨基吡啶对钾通道的阻断的影响。此外,高剂量的GABA受体拮抗剂荷包牡丹碱只能部分阻断这些作用:实际上,GABA受体激动剂蝇蕈醇的作用可与γ-羟基丁酸酯的作用区分开来,因为后者对钡离子的应用敏感。结果表明,γ-羟基丁酸酯的作用是增加钙的利用,这反过来又导致钙依赖性事件的启动。关于γ-羟基丁酸酯这些作用的功能后果,讨论了其可能的内源性调节作用。