Studies on convulsants in the isolated frog spinal cord. I. Antagonism of amino acid responses.

1. The isolated frog spinal cord was used to study the effects of picrotoxin, bicuculline, and strychnine on the responses of primary afferents to amino acids. Recording was by sucrose gap technique. 2. A series of neutral amino acids was found to depolarize primary afferents. Optimal activity was obtained by an amino acid whose carboxyl and amino groups were separated by a three-carbon chain length (i.e. GABA). Amino acids with shorter (i.e. beta-alanine, glycine) or longer (i.e. delta-aminovaleric acid, epsilon-aminocaproic acid) distances between the charged groups were less potent. Imidazoleacetic acid was the most potent depolarizing agent tested. 3. Picrotoxin and bicuculline antagonized the primary afferent depolarizations of a number of amino acids tested with equal specificity. Depolarizing responses to standard (10- minus 3 M) concentrations of beta-alanine and taurine were completely blocked by these convulsants, while depolarizations to 10- minus 3 gamma-aminobutyric acid (GABA) were only partially antagonized. Glycine responses were unaffected by these agentsk; Strychnine completely blocked beta-alanine and taurine depolarizations and incompletely antagonized several other neutral amino acids. GABA, glutamate, and glycine depolarizations were not affected. 5. These results suggest that there are at least three distinct populations of neutral amino acid receptors on primary afferent terminals: a GABA-like receptor, a taurine/beta-alanine receptor, and a glycine-like receptor. The strychnine resistance of the glycine responses indictaes that the primary afferent receptors for glycine differ from those on the somata of spinal neurones.