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.