Macro- and microscopic analysis of glycine-gated response in isolated CNS neurons.

利用“浓度钳”技术研究了甘氨酸诱导电流的药理学特性和动力学，该技术可以在单电极电压钳下进行内部灌注和快速应用外源溶液，并从年轻和成年大鼠中急性分离出单个下丘脑腹内侧（VMH）神经元。甘氨酸诱导电流在Cl^-平衡电位处发生逆转（E_<Cl>），细胞外Cl^-浓度的10倍变化导致甘氨酸逆转电位移位53 mV。甘氨酸诱导的Cl^-电流呈浓度依赖性显著增加，在Hill系数为1.8时，K_d为9 × 10^<-5> M。甘氨酸诱导的电导在膜电位大于-50 mV时表现出明显的电压依赖性，当超极化超过-110 mV时达到稳态值。甘氨酸诱导反应的激活和失活阶段都用双指数函数来描述。随着浓度的增加，离子（分别为快离子和慢离子）的增加。4个时间常数均随甘氨酸浓度的增加而减小。士的宁和微毒素对甘氨酸反应的阻断是非竞争性的。士的宁选择性地拮抗了α -氨基酸和β -氨基酸的反应，但不受双管碱或牛磺酸拮抗剂TAG的影响，这表明α -氨基酸和β -氨基酸激活了相同的甘氨酸受体。有机钙阻滞剂对VMH神经元低阈值（t型）钙通道的药理作用不同于周围神经节细胞和培养神经元。用浓度钳技术研究了gaba诱导的大鼠浦肯野细胞Cl^-电流。GABA受体的药理学性质与以往报道的其他制剂基本相似。在离体孤核神经元中，甘氨酸激活NMDA受体，而不是阻止细胞中NMDA受体的脱敏。少

Pharmacological properties and kinetics of glycine-induced currents were investigated in single ventromedial hypothalamic (VMH) neurons acutely isolated from young and adult rats by the use of a 'concentration-clamp' technique, which allows both internal perfusion and rapid application of an external solution under single-electrode voltage-clamp. The glycine-induced current reversed at the Cl^- equilibrium potential (E_<Cl>), and a ten-fold change of extracellular Cl^- concentration resulted in a 53 mV shift of the glycine reversal potential. Glycine-induced Cl^- currents increased sigmoidally in a concentration-dependent manner with a K_d of 9 x 10^<-5> M at the Hill coefficient of 1.8. The glycine-induced conductance exhibited a striking voltage dependency at membrane potentials more negative than -50 mV and reached a steady state value when hyperpolarized beyond -110 mV. Both the activation and inactivation phases of glycine-induced response are described by double exponential funct … More ions (fast and slow components, respectively) with the concentrations used. All four time constants decreased with increasing glycine concentration. The blockade of the glycine response by strychnine and picrotoxin was noncompetitive. The responses to individual alpha- and (bata-amino acids were selectively antagonized by strychnine, but were not affected by bicuculline or a taurine antagonist, TAG, suggesting that alpha-and beta-amino acids activate the same glycine receptor. The pharmacological properties of low-threshold (T-type) Ca channels of VMH neurons for organic Ca blockers differed from those of peripheral ganglion cells and cultured neurons. The GABA-induced Cl^- current in rat isolated Purkinje cells was also investigated by concentration-clamp technique. The pharmacological property of GABA receptor was basically similar to that previously reported in other preparations. In isolated nucleus tructus solitarii neurons, glycine initiates the activation of NMDA receptors rather than that glycine prevents the desensitivation at NMDA receptors in the cells. Less