Two rapid phases of GABA receptor desensitization, which proceeded with a 10-fold difference in rates, were detected in two types of experiment with membrane vesicle preparations from rat cerebral cortex. (i) The time course of GABA-mediated 36Cl− influx progressed in two phases. (ii) The 36Cl− influx was decreased, by preincubation with GABA, in two phases. Measurements were made in the time range 10–1000 ms. The major loss of channel opening activity occurred in the faster phase, which was complete in 100 ms with saturating GABA concentrations. The remaining activity decreased in a slower phase in a few seconds with a 10-fold slower rate. The faster phase of desensitization was more than 10-fold faster than previously observed and the slower phase was slightly faster than previously reported measurements with GABA receptor. Both desensitization processes had a similar dependence on GABA concentration with a half response at ∼ 100 μM GABA.
