Analysis of Mauthner cell responses to iontophoretically delivered pulses of GABA, glycine and L-glutamate.

1. The intracellularly recorded responses of goldfish Mauthner neurones to iontophoretically applied pulses of amino acids have been analysed: their time courses have been compared with each other, and with those predicted from diffusion theory.2. The rise time of the response to GABA is slower than that to glycine or L-glutamate. The response curves of the latter substances were very similar, and unlike that of GABA were markedly affected by increasing the distance of pipette-tip from the membrane. The results suggest that the time course of the responses to glycine and L-glutamate are determined mainly by free diffusion in the brain tissue (at least within about 200 mum of the cell), while that to GABA must be rate-limited by other factors, e.g. drug-receptor activation time.3. The possibility that the responses are influenced by some desensitizing process was investigated by applying a second (test) drug pulse during the response to a prior conditioning one. In the case of glycine and of L-glutamate there was no attenuation of the response to a second pulse at any time. With GABA, however, the second response was reduced during the period of the conditioning response; the reduction was progressively less marked the later the test pulse occurred. A similar effect with GABA was seen when glycine was used as the test pulse. The responses to long-maintained drug pulses also indicated that for GABA, but not for glycine or glutamate, there seems to be some desensitizing process present.4. Calculated time courses of responses to brief pulses of glycine and of L-glutamate (based upon diffusion theory) differed somewhat from the observed curves, largely during the falling phase. However, when the calculations were based upon second-order reactions (two molecules of drug per receptor) the diffusion model gave results very like the observed ones.5. Possible implications of these results for the role these three amino acids may have as neuro-transmitters are mentioned.