Title: EFFECTS OF <i>N</i>‐METHYLAMINO ACIDS AND CONVULSANTS ON SPONTANEOUS ACTION POTENTIALS IN GUINEA‐PIG CEREBELLAR SLICES
Abstract: N ‐methyl‐γ‐aminobutyrate ( N ‐methylGABA), N ‐methylglycine, N ‐methyltaurine and N ‐methylβ‐alanine diminished the frequency of spontaneous spike discharges in guinea‐pig cerebellar slices. Usually a weak excitatory effect preceded the inhibition. The inhibitory effects of N ‐methylGABA and N ‐methylβ‐alanine were competitively antagonized by both picrotoxin and strychnine. The inhibitory action of N ‐methyltaurine was competitively suppressed by strychnine and by low concentrations of picrotoxin. The inhibitory action of N ‐methylglycine was suppressed by strychnine but not by picrotoxin. The suppression was competitive at low concentrations of strychnine. N ‐methyl dl ‐glutamate brought about a strong inhibition followed by a strong excitation of the neurones. The inhibitory effects were competitively suppressed by both picrotoxin and strychnine. Neither convulsant affected the excitation. Whereas l ‐ or D‐glutamate caused only excitation in the majority of cells examined, a small proportion of the cells exhibited inhibition preceding the excitation by l ‐ or D‐glutamate. Such inhibitory effects were suppressed by picrotoxin but not by strychnine. Kinetic analyses of the dose‐response curves for the N ‐methylamino acid in the presence or absence of the convulsant indicated that the number of molecules of the amino acid combining with the receptor site to produce a response was 3 for N ‐methylGABA, 2 for N ‐methylglycine, 3 for N‐ methyltaurine, 3 for N ‐methylβ‐alanine. The corresponding value was 1 for N ‐methyl dl ‐glutamate (inhibition). The number of molecules of convulsant combining with the receptor site was calculated to be 2 for picrotoxin with N ‐methylGABA, N ‐methylβ‐alanine and N ‐methyl dl ‐glutamate and 1 for strychnine with all N ‐methylamino acids examined.