Membrane potential modulates the activation of GABA-gated channels.

1. The activity of single gamma-aminobutyric acid (GABA)-gated Cl- channels (GABA = 0.5-2.0 microM) was recorded in inside-out patches of membrane from cultured chick cerebral neurons. 2. The distribution of open intervals of the GABA channel was described by the sum of two exponentials, which suggests the presence of at least two open states of the channel. The time constants of these two components were 0.39 +/- 0.1 and 2.1 +/- 0.9 ms (+/- SD, n = 9). 3. The distribution of shut intervals was described by the sum of either three (n = 5) or four (n = 3) exponentials. This suggests the presence of at least three or four shut states. 4. At all GABA concentrations examined, the activity of the GABA channel decreased over time. This decline in activity was most likely the result of desensitization of the GABA channels. 5. The distribution of open intervals was unchanged during desensitization of the GABA channel. Thus desensitization is not associated with an alteration in either the mean lifetime of the two open states or the relative number of transitions to these two states. Rather, desensitization results from a decrease in the probability of channel opening. 6. There was an e-fold increase in the probability of finding a GABA channel open for every 80 +/- 43 mV (n = 4) of depolarization. The degree of voltage dependence decreased as the GABA channels desensitized. 7. The depolarization-induced increase in open channel probability was not associated with any change in the distribution of open intervals. Thus depolarization does not affect the mean open time of the channel but rather increases the likelihood that it will open. 8. A simple model with three or four shut and two open states is considered for the gating of the GABA channel by the agonist. Possible sites for the voltage dependence within this proposed model are discussed.