Cyclic ADP ribose-dependent ca 2+ release by group i metabotropic glutamate receptors in acutely dissociated rat hippocampal neurons

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 Ca 2+. In this study, we characterized the cellular mechanisms underlying Ca 2+ 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 Ca 2+ from ryanodine-sensitive stores via cyclic adenosine diphosphate ribose (cADPR), while the PLC/IP 3 signaling pathway was not involved in Ca 2+ mobilization. The application of glutamate, which depolarized the membrane potential by 28.5±4.9 mV (n = 4), led to transient Ca 2+ mobilization by mGluR5 and Ca 2+ influx through L-type Ca 2+ channels. We found no evidence that mGluR5-mediated Ca 2+ release and Ca 2+ influx through L-type Ca 2+ channels interact to generate supralinear Ca 2+ transients. Our study provides novel insights into the mechanisms of intracellular Ca 2+ mobilization by mGluR5 in the somata of hippocampal neurons. © 2011 Sohn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.