Fig. 5: Model II: Two desensitized subunits are required to occlude the pore.

a Model II builds upon Model I by adding one key hypothesis: receptors with only one subunit in its desensitized conformation are still conducting, and desensitization occurs when at least two subunits are desensitized. Thus, states AD₃, AD_4, and AD₅ are open states from a functional point of view. b In Model II, mutation of a subunit can affect both its desensitization and recovery, as shown here with an example in which both SU4 and SU5 are mutated (construct C⁴⁵): c₄⁺ and c₅⁺ reflect the increase in desensitization rates, c₄⁻ and c₅⁻ reflecting the increase in recovery rates. c Simulated currents for C^WT, C⁴ and C⁴⁵. d Representative currents for C^WT and C³ in black, are compared to their simulation counterparts in red. e–g Bar graphs summarizing the experimental data (in black) vs the simulations (in red) for the indicated concatemers on the kinetics (panel e) and the amplitude (panel f) of the fast desensitization component as well as the residual current after a 1 min long application of 10 mM GABA (panel g). Experimental data are shown as means (bar graphs) and standard deviations (error bars), with individual data points indicated as circles. Note that the results for the C⁵ construct are not displayed, since the experimental data are almost identical to that of C⁴ (see Fig. 2) and since the simulations for C⁴ and C⁵ are identical (see Supplementary Table 3). See Supplementary Fig. 5 for all simulation results; Supplementary Table 1 for numerical experimental values, the number of cells and number of independent series of experiments; and Supplementary Table 3 for the numerical values of parameters.