FIGURE 9.

State-dependent changes in accessibility in the thumb domain. A, pH dependence of A344C channel desensitization. Whole-cell currents were elicited in oocytes expressing A344C channels by extracellular acidification from solutions of pH 7.0 or 8.0 to a solution of pH 5.0 (n = 5). Note that A344C channels reside in the desensitized state at pH 7.0 because they do not respond to extracellular acidification. B, chemical modification by MTSET of A344C channels in the resting and desensitized states. Whole-cell currents were elicited by a change in extracellular pH from 8.0 to 5.0 before and after treatment with MTSET reagents for 15, 30, 60, or 120 s. MTSET was applied at pH 7.0 (open circles), i.e. channels in the desensitized state, or at pH 8.0 (blue circles), i.e. channels in the resting state. The peak current elicited by extracellular acidification after MTSET treatment was normalized to the peak current elicited by extracellular acidification before treatment. To determine statistical significance, the confidence intervals for the time constants of modification were compared. The time constants of modification at pH 7.0 (mean 39.9, CI 32.5–51.6) and pH 8.0 (mean 23.9, CI 20.4–28.8) were statistically different (p < 0.05, n = 13–33).