POTENTIATION OF A METABOTROPIC GLUTAMATERGIC RESPONSE FOLLOWING NMDA RECEPTOR ACTIVATION IN RAT HIPPOCAMPUS

Interactions between metabotropic glutamate and N-methyl-D-aspartate ( NMDA) receptor-mediated responses were investigated in hippocampal CA3 cells using the single-electrode voltage-clamp method. Bath applicati on (2.5-10 mu M, 30 s) or iontophoresis of 1-amino-cyclopentyl-trans-1 S,3R-dicarboxylate (ACPD), a selective agonist for metabotropic glutam ate receptors, resulted in an inward current associated with a decreas e in membrane conductance. Following transient bath application of NMD A (5-10 mu M, 30-60 s), the ACPD-induced inward current was potentiate d for a period of up to 25 min (by 61+/-8% with bath application, by 3 2+/-15% with iontophoresis). Transient application of NMDA did not res ult in a potentiation of ionotropic lpha-amino-3-hydroxy-5-methyl-4-is oxazolepropionic acid (AMPA) or metabotropic muscarinic responses. ACP D responses were not potentiated following transient AMPA application. Intracellular buffering of calcium with tetrapotassium bis(O-aminophe noxy)ethane-N,N,N',N'-tetraac etic acid (BAPTA) prevented potentiation by NMDA in all cells. Bath application of arachidonic acid did not mi mic the NMDA-induced potentiation. These results demonstrate that acti vation of NMDA receptors can specifically induce a long-lasting potent iation of a metabotropic glutamatergic response in hippocampal CA3 pyr amidal cells. The characterization of this interaction may contribute to the elucidation of the physiological significance of metabotropic g lutamate receptors.