Modulation of intracellular calcium mobilization and GABAergic currents through subtype-specific metabotropic glutamate receptors in rat hippocampus

Abstract

Among metabotropic glutamate receptors (mGluRs), type I mGluR modulates neuronal excitability through intracellular Ca²⁺ mobilization. Difference in Ca²⁺ mobilization between subclasses of the receptors has been reported, and this difference probably causes various neuronal modifications. In hippocampal interneurons, type I mGluRs (mGluR1 and mGluR5) have been immunohistochemically identified. The subclass-specific physiological effects of mGluRs on hippocampal synaptic transmission, however, have not been fully elucidated. In the present study, effect of type I mGluR agonist on intracellular Ca²⁺ concentration was investigated in slice preparation. DHPG increased intracellular Ca²⁺ concentration in hippocampal nonprincipal cells, and the Ca²⁺ elevation was partially inhibited by mGluR1-subtype-specific antagonist, CPCCOEt, or mGluR5-specific antagonist, MPEP. To examine the contribution of this DHPG-induced increment of cell excitability to inhibitory GABAergic signal transduction, spontaneous IPSCs (sIPSCs) were recorded from CA3 pyramidal neurons. Frequency and amplitude of sIPSCs were increased by DHPG application. This facilitation was prevented by CPCCOEt. In the absence of DHPG, perfusing CPCCOEt also inhibited sIPSCs. MPEP treatment does not markedly inhibited DHPG-induced facilitation of the sIPSCs. These results suggest that both subtypes of mGluRs are functionally expressed, and at least mGluR1 modulates IPSCs in this hippocampal area. [J Physiol Sci. 2008;58 Suppl:S128]