FIGURE 6.

Attachment of moieties at selected sites in the finger-thumb and β-ball-thumb interfaces accelerates desensitization. A and B, effect of MTSET treatment on the rates of desensitization of channels bearing Cys substitutions in the finger (A) and thumb (B) domains. Whole-cell currents were evoked by a change in extracellular pH from 8.0 to 5.0 before and after MTSET treatment. The time constants of desensitization were estimated by fitting the current decay after extracellular acidification from 8.0 to 5.0 to a single exponential function as described under “Experimental Procedures.” Statistically significant differences with the untreated control are indicated. *, p < 0.05; **, p < 0.01; +, p < 0.001 (n = 9–36) (t test). Statistically significant differences in the time constant of desensitization between untreated mutant channels and controls (ASIC1a C70L) are indicated in red (Kruskal-Wallis test followed by Dunn's multiple comparisons test). C, Helical wheel representation of positions in the α5 helix where the introduction of Cys mutation and MTSET treatment alter the rates of desensitization (yellow). Negatively charged and positively charged amino acids are notated in red and blue, respectively.