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

点击翻译按钮获取中文摘要

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.