Characterization of modulatory effects of postsynaptic metabotropic glutamate receptors on calcium currents in rat nucleus tractus solitarius

It is well known that metabotropic glutamate receptors (mGluRs) have multiple actions on neuronal excitability mediated by G-protein-coupled receptors, although the exact mechanisms by which these actions occur are not understood. This study examines the effects of mGluRs agonists on voltage-dependent Ca2+ channels (VDCCs) currents (I-Ca) in the nucleus tractus solitarius (NTS) of rats using patch-clamp recording methods. An application of (RS)-3,5-dihydroxyphenylglycine (DHPG, Group I mGluR agonist) caused both facilitation and inhibition of L-type and N/P/Q-types I-Ca, respectively. Neither (2S, 2'R, 3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine (DCG, Group II mGluRs agonist) nor L-(+)-2-amino-4-phosphonobutyric acid (AP-4, Group III mGluRs agonist) nor (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, mGluR5 agonist) modulated I-Ca. Intracellular dialysis of the G(i)-protein antibody and Gi-protein antibody attenuated the DHPG-induced facilitation and inhibition, respectively. The phospholipase C (PLC) inhibitor, as well as inhibition of either the protein kinase C (PKC) or inositol-1,4,5-trisphosphate (IP3) attenuated the DHPG-induced facilitation of ICa but not a DHPG-induced inhibition. Application of a strong depolarizing voltage prepulse attenuated the DHPG-induced inhibition of ICa. These results indicate that mGluR1 facilitates L-type VDCCs via G(q/11)-protein involving PKC including IP3 formation. On the other hand, mGluR1 inhibits N- and P/Q-types VDCCs via G(i)-protein betagamma subunits. (C) 2004 Elsevier B.V. All rights reserved.