Williams S R, Turner J P, Crunelli V
Department of Physiology, University of Wales College of Cardiff, U.K.
Neuroscience. 1995 May;66(1):133-41. doi: 10.1016/0306-4522(94)00604-4.
The actions of gamma-hydroxybutyrate, a drug known to lead to an increase in nocturnal slow wave sleep and induce epileptic states following systemic application, on the membrane properties of thalamocortical neurons from brain slices of the rat and cat dorsal lateral geniculate nucleus were studied using sharp electrode intracellular recordings. Gamma-hydroxybutyrate applied by addition to the perfusion medium led to a concentration-dependent and reversible hyperpolarization of the membrane potential accompanied by a decrease in apparent input resistance (0.1 mM: 2.3 +/- 0.3 mV, 9.5 +/- 1.0%; 10 mM: 11.3 +/- 1.3 mV, 37.5 +/- 10.8%, respectively). In six of seven neurons the iontophoretic or bath (0.1-0.2 mM) application of low concentrations of gamma-hydroxybutyrate led to a hyperpolarization accompanied by the appearance of low-frequency (< 4 Hz) membrane potential oscillations crowned by bursts of action potentials, when the membrane potential of these neurons was initially set depolarized to the range where ongoing oscillatory activity occurred. The gamma-hydroxybutyrate-elicited hyperpolarization was reversibly antagonized by the co-application of the GABAB receptor antagonist CGP 35348 (0.4-1 mM), but was not affected by the putative gamma-hydroxybutyrate receptor antagonist NCS 382 (0.1-5 mM) or tetrodotoxin (1 microM), suggesting that gamma-hydroxybutyrate tonically activates postsynaptic GABAB receptors. The gamma-hydroxybutyrate-induced promotion of oscillatory activity and action potential burst firing of thalamocortical neurons may be one mechanism by which gamma-hydroxybutyrate leads to an increase in the deep stages of sleep and the generation of electroencephalogram and behavioural patterns typical of absence epilepsy.
γ-羟基丁酸是一种已知会导致夜间慢波睡眠增加并在全身应用后诱发癫痫状态的药物。本研究使用尖锐电极细胞内记录法，研究了γ-羟基丁酸对大鼠和猫背外侧膝状核脑片丘脑皮质神经元膜特性的影响。通过向灌注培养基中添加γ-羟基丁酸，可导致膜电位呈浓度依赖性且可逆的超极化，并伴有表观输入电阻降低（分别为0.1 mM：2.3±0.3 mV，9.5±1.0%；10 mM：11.3±1.3 mV，37.5±10.8%）。在七个神经元中的六个中，当这些神经元的膜电位最初被去极化到正在进行振荡活动的范围时，离子电渗法或浴用（0.1 - 0.2 mM）低浓度的γ-羟基丁酸会导致超极化，并伴有低频（<4 Hz）膜电位振荡的出现，这些振荡以动作电位爆发为顶点。γ-羟基丁酸引起的超极化可被共同应用GABAB受体拮抗剂CGP 35348（0.4 - 1 mM）可逆性拮抗，但不受假定的γ-羟基丁酸受体拮抗剂NCS 382（0.1 - 5 mM）或河豚毒素（1 μM）的影响，这表明γ-羟基丁酸可持续性激活突触后GABAB受体。γ-羟基丁酸诱导丘脑皮质神经元振荡活动增强和动作电位爆发发放，可能是γ-羟基丁酸导致睡眠深度增加以及产生失神癫痫典型脑电图和行为模式的一种机制。
