TABLE 3.

Equilibrium co-agonist model parameters for wild-type and α1M236Cβ2γ2L GABA_A receptors

Results are from nonlinear least squares fits to Equation 3, which describes an allosteric two-state equilibrium mechanism with two classes of agonist sites (one for GABA and one for etomidate), each with two equivalent sites (10). L₀ is a dimensionless basal equilibrium gating variable, inversely related to spontaneous activity. For wild-type receptors, spontaneous activity was undetectable, and we constrained L₀ to a previous estimate (25,000) for wild type (32). K_G and K_E are equilibrium dissociation constants for GABA and etomidate binding to inactive states, and c and d are dimensionless parameters representing the respective ratios of binding constants in active versus inactive states. The agonist efficacies of GABA and etomidate are inversely related to c² and d², respectively.

Receptor	L0	KG	c	KE	d
		μm		μm
α1β2γ2L	25,000	70 ± 22	0.0019 ± 0.00038	40 ± 14	0.0076 ± 0.0010
α1M236Cβ2γ2L	200a	100 ± 19	0.135 ± 0.0070a	70 ± 22	0.014 ± 0.0046

^a Differs from wild-type value at p < 0.01.