C, O and D represent closed, open and desensitized states. C is in the resting state, CH+ are in partially activated states, and CnH+ is the opening-permissive state. In hASIC1a, the transitions between C states are H+ dependent, indicated by f[H+]. The wild-type ASIC1a open state completely desensitizes as indicated by the thick arrow that in this scheme means a high value for the rate constant kODo (transition from OH+ to DOH+). Pre-open channels (CH+) -those that make the most abundant population at low proton concentrations (pH range 7.2 to 7.0) when not all subunits within a trimer are protonated- and CnH+ undergo strong SSD (thick arrows). For Q276 mutants, specifically Q276G, the rate constants leading to desensitization –kODo and kCDc- are markedly reduced that is channels exhibit very long opening events and are resistant to SSD.