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

分离的中枢神经系统神经元甘氨酸门控反应的宏观和微观分析。

基本信息

批准号：
63480107
负责人：
AKAIKE Norio
金额：
$ 3.58万
依托单位：
TOHOKU UNIVERSITY (1989)Kyushu University (1988)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

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

通过使用“浓差钳”技术从年轻和成年大鼠中急性分离出单个腹内侧下丘脑（VMH）神经元，研究了甘氨酸诱导电流的药理学特性和动力学，该技术允许内部灌注和快速应用外部溶液在单电极电压钳下，甘氨酸诱导的电流在 Cl^- 平衡电位 (E_<Cl>) 下反转，并且细胞外 Cl^- 浓度发生十倍的变化。导致甘氨酸诱导的Cl^-电流以浓度依赖方式S形增加53mV，希尔系数为1.8，K_d为9×10^-5M。感应电导在膜电位负于-50 mV 时表现出惊人的电压依赖性，并在超极化超过-110 mV 时达到稳态值。甘氨酸诱导的反应的失活阶段用双指数函数（分别是快离子和慢离子）来描述，所有四个时间常数都随着甘氨酸浓度的增加而降低。非竞争性的。对单个α-和bata-氨基酸的反应被士的宁选择性拮抗，但不受荷包牡丹碱或牛磺酸拮抗剂的影响， TAG，表明 α- 和 β- 氨基酸激活相同的甘氨酸受体。有机 Ca 阻滞剂的 VMH 神经元低阈值（T 型）Ca 通道的药理学特性与外周神经节细胞和培养神经元的药理学特性不同。还通过浓度钳技术研究了大鼠分离的浦肯野细胞中诱导的Cl^-电流。GABA受体的药理学特性与先前在分离的核结构中报道的基本相似。在孤寂神经元中，甘氨酸启动 NMDA 受体的激活，而不是阻止细胞中 NMDA 受体的脱敏。