cASIC1 Q277G exhibits strong desensitization over several pH values. (A) Structure of the cASIC1 resting state (PDB accession no. 6VTL). Domains are identified by color in one subunit while the remaining two subunits are colored light or darker gray. (B) Close in view of the boxed region in A showing Q277 position in two subunits as well as functionally relevant amino acids. The “front” subunit has been removed, leaving only the colored and “rear” subunits for clarity. (C) Peak normalized outside-out patch responses from cASIC1 WT (black trace) or Q277G (red trace) during a jump from pH 8.0 to pH 5.5. (D and E) Responses from single outside-out cASIC1 WT (D) or Q277G (E) patches to the indicated pH stimuli. (F) Summary of the percent steady-state current, normalized to the peak response within a pH, over several patches. The holding potential was −60 mV. Circles denote individual patches, and error bars show SEM.