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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

甘氨酸诱导的电流的药理学特性和动力学进行了研究，在单一的腹内侧下丘脑（VMH）神经元急性分离的年轻和成年大鼠通过使用“浓度钳”技术，它允许内部灌注和快速应用程序下的外部解决方案单电极电压钳。甘氨酸诱导的电流在Cl^-平衡电位（E_）处发生逆转<Cl>，细胞外Cl^-浓度的10倍变化导致甘氨酸逆转电位移动53 mV。甘氨酸诱导的Cl^-电流以浓度依赖性方式呈S形增加，在希尔系数为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时表现出显著的电压依赖性，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均可用双指数函数描述， ...更多信息离子（分别为快和慢分量）与所用浓度。所有四个时间常数随甘氨酸浓度的增加而降低。士的宁和印防己毒素对甘氨酸反应的阻断是非竞争性的。士的宁可选择性拮抗α-和β-氨基酸的反应，但荷包牡丹碱或牛磺酸拮抗剂TAG不影响α-和β-氨基酸激活相同的甘氨酸受体。VMH神经元的低阈值（T型）钙通道的药理学特性与周围神经节细胞和培养的神经元不同。用浓度钳技术观察GABA诱导的大鼠浦肯野细胞Cl^-电流。GABA受体的药理学性质与文献报道的其他制剂基本相似。在离体的孤束核神经元中，甘氨酸启动NMDA受体的激活，而不是甘氨酸阻止细胞中NMDA受体的脱敏。少