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.

为了分析对代谢型谷氨酸受体（MGLUR）刺激的神经元反应，我们将Nystatin穿孔贴片记录应用于未成熟大鼠的急性解离神经元。 1。在CA1锥体神经元中，我们发现1）MGLUR激活通过开放Ca2+依赖性K+通道的中间电导类型的开口导致了外部电流，2）MGlur对激动剂的亲和力比其激动剂的亲和力比抑制抑制剂Mgglus and putited Mgglu and aptogagogain and aptair mg and aptogrus aptogrus aptogrus，反应，4）mglur激活后G蛋白（> sy.gtoreq。>）磷脂酶C（> sy.gtoreq。>）IP3生产（> sy.gtoreq。> sy.gtoreq。）Ca2+从胞内存储（> sy.gtoreq> sy.gtoreq。>）开放Ca2+ -depandent k k k的细胞内存储（> sy.gtoreq。）。 2。在CA3锥体神经元中，向内缓慢的电流是主要反应，仅在40％的细胞中观察到外向电流。据澄清，1）慢的内向电流基于对M电流的抑制，2）与激动剂相比，对激动剂的亲和力比向外电流高10倍，3）仅由TACPD诱导的外流电流（但不是由quisqualic Acid）被AP3和AP4.3和AP4.3。在齿状颗粒细胞中，外部电流的持续时间比CA1中的电流更长，并且慢速向内电流被AP3.4逆转抑制。在1-至2周大的大鼠中，来自CA1腹侧1/3的80％细胞中观察到MGLU反应，但在背侧1/3的40％的细胞中。当大鼠年龄为3至4周时，在腹侧1/3中，观察频率降低至40％，背侧1/3的观察频率降低到5％。这些结果表明，MGLU反应显示区域差异和个体发生变化。预计MGLU反应的这些潜水员的作用将极大地影响神经元令人兴奋，这是理解中枢神经系统中神经元网络必不可少的信息。