Effects of N-methylamino acids and convulsants on spontaneous action potentials in guinea-pig cerebellar slices.

1. N-methyl-gamma-aminobutyrate (N-methylGABA), N-methylglycine, N-methyltaurine and N-methylbeta-alanine diminished the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Usually a weak excitatory effect preceded the inhibition. 2. The inhibitory effects of N-methylGABA and N-methylbeta-alanine were competitively antagonized by both picrotoxin and strychnine. 3. The inhibitory action of N-methyltaurine was competitively suppressed by strychnine and by low concentrations of picrotoxin. 4. The inhibitory action of N-methylglycine was suppressed by strychnine but not by picrotoxin. The suppression was competitive at low concentrations of strychnine. 5. N-methylDL-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. 6. 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. 7. 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-methylbeta-alanine. The corresponding value was 1 for N-methylDL-glutamate (inhibition). The number of molecules of convulsant combining with the receptor site was calculated to be 2 for picrotoxin with N-methylGABA, N-methylbeta-alanine and N-methylDL-glutamate and 1 for strychnine with all N-methylamino acids examined.