cyclic adp ribose-dependent ca2+ release by group i metabotropic glutamate receptors in acutely dissociated rat hippocampal neurons循环adp ribose-dependent ca2 +释放组我metabotropic敏锐地分离大鼠海马神经元谷氨酸受体.pdfVIP

Cyclic ADP Ribose-Dependent Ca2+ Release by Group I Metabotropic Glutamate Receptors in Acutely Dissociated Rat Hippocampal Neurons 1¤ 1 1 2 1 1 Jong-Woo Sohn , Weon-Jin Yu , Doyun Lee , Hee-Sup Shin , Suk-Ho Lee , Won-Kyung Ho * 1 Department of Physiology and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, Korea, 2 Center for Neural Science, Korea Institute of Science and Technology, Seoul, Korea Abstract Group I metabotropic glutamate receptors (group I mGluRs; mGluR1 and mGluR5) exert diverse effects on neuronal and synaptic functions, many of which are regulated by intracellular Ca2+. In this study, we characterized the cellular mechanisms underlying Ca2+ mobilization induced by (RS)-3,5-dihydroxyphenylglycine (DHPG; a specific group I mGluR agonist) in the somata of acutely dissociated rat hippocampal neurons using microfluorometry. We found that DHPG activates mGluR5 to mobilize intracellular Ca2+ from ryanodine-sensitive stores via cyclic adenosine diphosphate ribose (cADPR), while the PLC/IP3 signaling pathway was not involved in Ca2+ mobilization. The application of glutamate, which depolarized the membrane potential by 28.5 64.9 mV (n = 4), led to transient Ca2+ mobilization by mGluR5 and Ca2+ influx through L-type Ca2+ channels. We found no evidence that mGluR5-mediated Ca2+ release and Ca2+ influx through L-type Ca2+ channels interact to generate supralinear Ca2+ transients. Our study provides novel insights into the mechanisms of intracellular Ca2+ mobilization by mGluR5 i