L-homocysteic acid but not L-glutamate is an endogenous N-methyl-D-aspartic acid receptor preferring agonist in rat neocortical neurons in vitro.

The effects of ionophoretically applied L-homocysteate (L-HCA), L-glutamate (L-Glu) and N-methyl-D-aspartate (NMDA) were compared in rat neocortical neurons recorded intracellularly in vitro. The firing pattern and the time course of membrane depolarization induced by L-HCA resembled those of NMDA responses. Action potentials evoked by NMDA and L-HCA were superimposed upon slow depolarizations in a burst-like pattern, while L-Glu elicited single spike discharges. Ionophoretically applied D-2-amino-5-phosphonovalerate (2-APV) at doses sufficient to abolish NMDA responses, markedly reduced the L-HCA induced depolarizations but had no detectable effect on the L-Glu responses. The present findings are consistent with a possible role of L-HCA as an NMDA receptor preferring neurotransmitter in the rat frontal cortex.