Activation of subconductance states by gamma-aminobutyric acid and its analogs in chick cerebral neurons.

The action of gamma-aminobutyric acid (GABA) and the GABAA-receptor agonists muscimol, isoguvacine and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol (THIP) were studied at the single-channel level in outside-out membrane patches from cultured chick cerebral neurons. All agonists activated channels with multiple-conductance states. The main-state conductance activated by all agonists had a value around 26 pS in symmetrical TRIS/Cl solutions. Subconductance states of around 13 pS and 18 pS were seen with application of each agonist. Muscimol and isoguvacine tended preferentially to activate subconductance states. Gating by all agonists was complex. Open-time distributions for main-state activity gated by GABA, isoguvacine and THIP were best described by the sum of two exponential curves with similar time constants. Muscimol-gated activity was best described by the sum of three exponentials indicating the presence of an additional longer open state. These results indicate that certain GABAA-receptor agonists are capable of preferentially activating subconductance states.