Fig. 3.
Activation properties of GABAergic agonists. Estimated open probability of the concatemeric β2α1γ2L + β2α1 GABAA receptor is given as a function of concentration of GABA, propofol (PRO), P4S, β-alanine (β-Ala), pentobarbital (PEB), or the steroids alfaxalone (ALF), 3α5αP, 3α5βP, ent-3α5βP, and etiocholanolone (Etio). The data points and error bars show mean ± S.D. from five to eight cells. The curves were generated by fitting eq. 1 to the Popen data (see Materials and Methods). The fitted values of K and c are provided in Table 1. The data for GABA (dashed line) and propofol (dotted line) are from prior reports (Akk et al., 2018; Shin et al., 2018). The effects of alfaxalone, 3α5αP, 3α5βP, and ent-3α5βP on the wild-type concatemeric receptor were obtained in the presence of a low concentration of GABA that generated a background response with a Popen value of ∼0.1 in wild-type concatemeric receptors. Introduction of the α1(L263S) mutation increases the constitutive open probability and mimics the presence of GABA. A receptor containing the α1(L263S) mutation in both concatemeric constructs was used to determine the activation properties of alfaxalone and etiocholanolone.