Differential effects of (D)- and (L)-homocysteic acid on the membrane potential of cat caudate neurons in situ.

The enantiomers of homocysteic acid have been applied by microiontophoresis to neurons of the cat caudate nucleus in situ. The (L)-enantiomer elicited a bursty firing pattern similar to the one caused by N-methyl-D-aspartate, but differing from the N-methyl-D-aspartate pattern inasmuch as (L)-homocysteate induced depolarization shifts were shorter and had a smaller amplitude. (L)-Homocysteate induced excitations could be strongly inhibited by the selective N-methyl-D-aspartate antagonist 2-amino-7-phosphonoheptanoic acid but they were less sensitive to this antagonist than N-methyl-D-aspartate itself. (D)-Homocysteate elicited a more regular firing pattern similar to the one caused by non-N-methyl-D-aspartate excitatory amino acids such as quisqualate. These excitations were only rarely inhibited by 2-amino-7-phosphonoheptanoic acid. Our results suggest that (L)-homocysteate, a transmitter candidate at central mammalian synapses, is a mixed excitatory amino acid agonist with a strong preference for N-methyl-D-aspartate receptors in the cat caudate nucleus, while (D)-homocysteate has a predominant action at non-N-methyl-D-aspartate excitatory amino acid receptors.