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METABOTROPIC GLUTAMATE RESPONSES IN PRE-AND POSTSYNAPTIC MEMBRANES -CROSSTALK IN THE SIGNAL TRANSDUCTION PATHWAYS-

突触前膜和突触后膜中的代谢性谷氨酸反应 - 信号转导途径中的串扰 -

基本信息

批准号：
04404023
负责人：
AKAIKE Norio
金额：
$ 8.32万
依托单位：
KYUSHU UNIVERSITY (1993)Tohoku University (1992)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

In order to analyze neuronal responses to metabotropic glutamate receptor (mGluR) stimulation, we applied nystatin perforated patch recording to acutely dissociated neurons of immature rats. 1. In CA1 pyramidal neurons, we have found that 1) mGluR activation led to an outward current through opening of Ca2+-dependent K+ channels of intermediate conductance type, 2) the affinity of mGluR for its agonists was 10- to 100-fold higher than that of ionotropic glutamate receptors, 3) the putative mGluR antagonists, AP3 and AP4, did not suppress mGlu responses, 4) mGluR activation is followed by G protein (〕SY.gtoreq.〔) phospholipase C (〕SY.gtoreq.〔) IP3 production (〕SY.gtoreq.〔) Ca2+ release from intracellular stores (〕SY.gtoreq.〔) opening of Ca2+-dependent K+ channels. 2. In CA3 pyramidal neurons, slow inward current was the dominant response, with outward current observed in only 40% of cells. It was clarified that 1) the slow inward current was based on suppression of M current, 2) slow inward currents showed 10-times higher affinity to agonists than outward currents, 3) only the outward currents induced by tACPD (but not by quisqualic acid) were blocked by AP3 and AP4.3. In dentate granule cells, the outward currents had longer duration than those in CA1 and the slow inward current was reversibly suppressed by AP3.4. mGlu response was observed in 80% of the cells from the ventral 1/3 of the CA1 in 1- to 2- week-old rats, but in 40% of the cells from the dorsal 1/3. Frequency of observation was reduced to 40% in the ventral 1/3 and 5% in the dorsal 1/3 when the rats were 3- to 4-week-old.These results suggest that mGlu responses show regional differences and ontogenetic changes. These diverse actions of mGlu responses are supposed to greatly affect neuronal excitability, an information indispensable for understanding neuronal networks in the CNS.

为了分析神经元对代谢型谷氨酸受体（mGluR）刺激的反应，我们应用制霉菌素穿孔膜片记录急性分离的未成年大鼠神经元。1.在CA 1锥体神经元中，我们发现：1）mGluR激活导致通过开放中间电导型Ca 2+依赖性K+通道的外向电流，2）mGluR对其激动剂的亲和力比离子型谷氨酸受体的亲和力高10- 100倍，3）假定的mGluR拮抗剂AP 3和AP 4不抑制mGlu反应，4）mGluR活化后是G蛋白（）SY ≥（）磷脂酶C（）SY ≥（）IP 3生产（）细胞内储存的Ca 2+释放（）SY.gtoreq.（）Ca ~（2+）依赖性K ~+通道开放。2.在CA 3锥体神经元中，慢内向电流是主要的反应，仅在40%的细胞中观察到外向电流。阐明了1）缓慢内向电流是基于M电流的抑制，2）缓慢内向电流显示出比外向电流高10倍的对激动剂的亲和力，3）只有tACPD（而不是使君子酸）诱导的外向电流被AP 3和AP 4.3阻断。在齿状回颗粒细胞，外向电流的持续时间比在CA 1和慢内向电流可逆地抑制AP 3.4。1- 2周龄大鼠CA 1腹侧1/3的细胞中有80%观察到mGlu反应，但背侧1/3的细胞中有40%观察到mGlu反应。3 ~ 4周龄时，腹侧1/3和背侧1/3的mGlu反应频率分别为40%和5%。mGlu反应的这些不同作用被认为极大地影响神经元兴奋性，这是理解CNS中神经元网络不可或缺的信息。