Fig. 3.
Modeling results from studies on human β3 homomeric receptors. (A) A simplified allosteric activation model based on Monod et al. (1965), Colquhoun (1998), Chang and Weiss (1999), and Rusch et al. (2004). The model describes receptor activation with five sites whose affinity to agonist (A) in the closed state is described by KC and in the open state by KO. LO (ratio of C to O) describes opening of unliganded receptors. Opening of fully liganded receptors is described by LO multiplied by d (= KO/KC) to the fifth power. (B) The data points show averaged values for open probability (Poest) of wild-type and mutant β3 receptors activated by propofol. The Poest values were obtained by comparing baseline current level and responses to propofol to a current range spanning from Po of 0 (determined in the presence of picrotoxin or blocking concentrations of pentobarbital) to Po of 1 (maximal inward current during or after application of pentobarbital). The curves were generated by fitting eq. 2 (with n = 5 sites) to the data. Fitting parameters are given in Table 3. (C) The data points show averaged values for open probability (Poest) of wild-type and mutant β3 receptors activated by pentobarbital. The Poest values were obtained by comparing baseline current level and responses to pentobarbital to a current range spanning from Po of 0 to Po of 1. The curves were generated by fitting eq. 2 (with n = 4 sites) to the Po data. Fitting parameters are given in Table 3.