Both mGluR1 and mGluR5 mediate Ca2+ release and inward currents in hippocampal CA1 pyramidal neurons.
Using combined whole-cell voltage-clamp recording and Ca2+ imaging we have investigated further the characteristics and pharmacology of group I metabotropic l-glutamate receptor (mGluR)-mediated responses in CA1 pyramidal neurons of the rat hippocampus. The selective group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), evoked a transient increase in intracellular Ca2+ levels ([Ca2+]i), within neuronal somas and apical dendrites, together with a relatively long lasting inward current (I(DHPG)). Both types of response were enhanced by depolarisation (-30 mV), and this condition was used for their characterisation. The DHPG-induced [Ca2+]i rise was much more sensitive to manipulations of Ca2+ homeostasis, such as using the Ca2+ store depleting agent, cyclopiazonic acid (50-100 microM), the fast Ca2+ buffer, BAPTA (intracellular; 20-40 mM) and Ca(2+)-free/EGTA (1 mM) bath solution, than I(DHPG), suggesting that these responses are, in the main part, mediated by distinct processes. The selective mGluR1 and mGluR5 antagonists, (S)-(+)-alpha-amino-a-methylbenzeneacetic acid (LY367385; 100 microM) and 2-methyl-6-(phenylethynyl)-pyridine (MPEP;10 microM), respectively, markedly inhibited both I(DHPG) and the DHPG-evoked increase in [Ca2+]i. Moreover, these antagonists inhibited the Ca2+ response by more than 50% suggesting a synergistic interaction between mGluR1 and mGluR5. This study demonstrates that in CA1 pyramidal neurons group I mGluR-mediated inward currents and Ca2+ release from intracellular stores are enhanced under depolarising conditions and that mGluR1 and mGluR5 both contribute to these phenomena.
Rae
Mark G
MG
Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK. m.g.rae@dundee.ac.uk
Irving
Andrew J
AJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D002118:Calcium