Premium
Group I metabotropic glutamate receptor‐mediated calcium signalling and immediate early gene expression in cultured rat striatal neurons
Author(s) -
Mao Limin,
Wang John Q.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02495.x
Subject(s) - metabotropic glutamate receptor , phospholipase c , metabotropic receptor , biology , striatum , glutamate receptor , agonist , metabotropic glutamate receptor 1 , nmda receptor , receptor , intracellular , medicine , microbiology and biotechnology , endocrinology , signal transduction , biochemistry , dopamine
Group I metabotropic glutamate receptors (mGluRs) are positively coupled to phospholipase C (PLC) via G αq ‐proteins and are expressed in the medium‐sized projection neurons of striatum. To characterize the group I mGluR/PLC‐sensitive modulation of intracellular Ca 2+ ([Ca 2+ ] i ) signalling, primary neuronal cultures were prepared from the striatum of E19 rat embryos or neonatal day‐1 rat pups. Cytoplasmic Ca 2+ signals were examined with fura‐2/AM at a signal cell level. After 17–18 days in culture, a profound Ca 2+ response consisting of two phases was induced in cultured striatal neurons following bath application of the selective group I agonist, 3,5‐dihydroxyphenylglycine (DHPG). The [Ca 2+ ] i elevation was concentration‐ and time‐dependent, and was blocked by coexposure to the group I antagonist, N ‐phenyl‐7‐(hydroxyimino)cyclopropa[b]chromen‐1a‐carboxamide (PHCCC), or the PLC inhibitor, U‐73122, but not to the group II/III antagonist ( RS )‐α‐methylserine‐ O ‐phosphate monophenyl ester (MSOPPE). A series of further pharmacological studies demonstrated that the initial spike‐like transient was dependent on intracellular Ca 2+ mobilization through 1,4,5‐triphosphate‐sensitive stores, and the second long‐lasting rise was dependent on extracellular Ca 2+ influx through N ‐methyl‐ d ‐aspartate (NMDA) receptors and especially L‐type voltage‐operated Ca 2+ channels. Lastly, using an immediate early gene c‐ fos as a report of inducible gene expression, the resultant [Ca 2+ ] i elevation contributes to DHPG‐stimulated c‐ fos mRNA and Fos protein expression in striatal neurons as revealed by quantitative in situ hybridization and immunocytochemistry, respectively. These results demonstrate that group I mGluRs are able to affect Ca 2+ homeostasis at multiple levels and trigger Ca 2+ ‐sensitive gene transcription in striatal neurons.