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，我们将制霉菌素穿孔贴片记录应用于未成熟大鼠的急性分离神经元 1。在 CA1 锥体神经元中，我们发现 1) mGluR 激活导致通过的外向电流。打开中等电导型 Ca2+ 依赖性 K+ 通道，2) mGluR 与其激动剂的亲和力为 10- 至比离子型谷氨酸受体高 100 倍，3) 假定的 mGluR 拮抗剂 AP3 和 AP4 不会抑制 mGlu 反应，4) mGluR 激活之后是 G 蛋白 (〕SY.gtoreq。〔) 磷脂酶 C (〕SY .gtoreq.〔) IP3 产生 (〕SY.gtoreq.〔) Ca2+ 释放细胞内储存 (]SY.gtoreq.〔) 打开 Ca2+ 依赖性 K+ 通道 2. 在 CA3 锥体神经元中，缓慢的内向电流是主要反应，仅在 40% 的细胞中观察到外向电流 1。 ) 缓慢的内向电流基于 M 电流的抑制，2) 缓慢的内向电流对激动剂的亲和力比外向电流高 10 倍，3) 仅外向电流tACPD 诱导的电流被 AP3 和 AP4.3 阻断，外向电流比 CA1 中的电流持续时间更长，并且缓慢的内向电流被 mGlu 反应可逆地抑制。在 1 至 2 周龄大鼠中，80% 的 CA1 腹侧 1/3 细胞中观察到这一现象，但 40% 的细胞中观察到当大鼠 3 至 4 周龄时，腹侧 1/3 的观察频率减少至 40%，背侧 1/3 的观察频率减少至 5%。这些结果表明 mGlu 反应表现出区域差异。 mGlu 反应的这些不同作用被认为会极大地影响神经兴奋性，这是理解中枢神经系统神经网络不可或缺的信息。