Mouginot D, Kombian S B, Pittman Q J
Neuroscience Research Group, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
J Neurophysiol. 1998 Mar;79(3):1508-17. doi: 10.1152/jn.1998.79.3.1508.
1508-1517, 1998. Whole cell recordings (nystatin-perforated patch) were carried out on magnocellular neurons of the rat supraoptic nucleus (SON) to study the modulation of inhibitory postsynaptic currents (IPSCs) by gamma-aminobutyric acid-B (GABAB) receptors. Field stimulation adjacent to the SON in the presence of kynurenic acid, evoked monosynaptic GABAergic IPSCs. Baclofen reversibly reduced the amplitude of the IPSCs in a dose-dependent manner (EC50: 0.68 microM) without apparent effect on the holding current (Vh = -80 mV) or input resistance and altered neither the kinetic properties, nor the reversal potential of IPSCs. Concomittant to IPSC depression, baclofen enhanced the paired-pulse ratio for two consecutive IPSCs [interstimulus interval (ISI): 50 ms], an effect consistent with a presynaptic locus of action. Both actions of baclofen were abolished by CGP35348 (500 microM), a GABAB receptor antagonist. In testing for involvement of synaptically activated presynaptic GABAB receptors, we only recorded paired-pulse facilitation at most ISIs tested (50-500 ms), suggesting that the classical GABAB autoreceptors may not normally be activated in our conditions. However, enhancement of local GABA concentration by perfusion of a GABA uptake inhibitor (NO-711) revealed an action of endogenous GABA at these presynaptic GABAB receptors. The nonselective K+ channel blocker Ba2+ abolished baclofen's effect and pertussis toxin (PTX) pretreatment (200-500 ng/ml for 18-24 h) was ineffective in blocking the baclofen-induced inhibition, making an involvement of PTX-sensitive G protein unlikely. The present results show that presynaptic GABAB receptors that are coupled to PTX-insensitive G-proteins may be activated by endogenous GABA under conditions of reduced GABA uptake, thus regulating the inhibitory synaptic input to SON.
1998年，第1508 - 1517页。采用全细胞记录法（制霉菌素穿孔膜片钳）对大鼠视上核（SON）的大细胞神经元进行研究，以探讨γ-氨基丁酸B（GABAB）受体对抑制性突触后电流（IPSCs）的调节作用。在犬尿氨酸存在的情况下，对视上核附近进行场刺激，诱发单突触GABA能IPSCs。巴氯芬以剂量依赖方式可逆性降低IPSCs的幅度（半数有效浓度：0.68微摩尔），对钳制电流（Vh = -80毫伏）或输入电阻无明显影响，既不改变IPSCs的动力学特性，也不改变其反转电位。与IPSC抑制同时，巴氯芬提高了两个连续IPSCs的配对脉冲比率[刺激间隔（ISI）：50毫秒]，这一效应与突触前作用位点一致。巴氯芬的这两种作用均被GABAB受体拮抗剂CGP35348（500微摩尔）消除。在测试突触激活的突触前GABAB受体的参与情况时，我们在大多数测试的ISI（50 - 500毫秒）下仅记录到配对脉冲易化，这表明在我们的实验条件下，经典的GABAB自身受体可能通常不会被激活。然而，通过灌注GABA摄取抑制剂（NO - 711）提高局部GABA浓度，揭示了内源性GABA对这些突触前GABAB受体的作用。非选择性钾通道阻滞剂Ba2+消除了巴氯芬的作用，百日咳毒素（PTX）预处理（200 - 500纳克/毫升，持续18 - 24小时）对阻断巴氯芬诱导的抑制无效，因此不太可能涉及对PTX敏感的G蛋白。目前的结果表明，与对PTX不敏感的G蛋白偶联的突触前GABAB受体可能在GABA摄取减少的情况下被内源性GABA激活，从而调节对视上核的抑制性突触输入。
