Fig. 1.

Mutation of β₂Arg207, α₁Arg67, or α₁Arg132 to alanine increases the rate of deactivation and right-shifts concentration-response curves but does not affect desensitization. A, homology model of the GABA_A receptor agonist binding site at the interface between β₂ (pink) and α₁ (yellow) subunits showing residues β₂Arg207, α₁Arg67, and α₁Arg132 (O'Mara et al., 2005; with α₁Arg67 rotated arbitrarily so as to protrude into the binding pocket). B, mutants and wild-type receptors were challenged with 2 to 4 ms (left) or 500 ms (right) pulses of 10 mM GABA (because of differences in EC₅₀, we ensured saturation by using 30 mM GABA for R67A). All traces were normalized to their peak to ease comparison. Peak currents of traces shown varied between 60 and 300 pA. Each trace is the average of between 8 and 25 sweeps, recorded while the patches were held at −60 mV. The top traces in both are example recordings from open pipette tips at the end of an experiment to demonstrate solution exchange. C, GABA concentration-response curves of peak currents, fit with the equation I_GABA/I_GABA-max = Y_max/[(EC₅₀/[GABA])^N + 1], where N is the Hill coefficient (Prism 4). Only two data points are shown for α₁β₂, which were linearly interpolated to estimate EC₅₀ (Table 2).