The amino terminus of acid-sensing ion channel 1a forms a reentrant 'loop' that frames the lower pore and harbors a conserved 'His-Gly' motif implicated in gating and ion selectivity mechanisms.
Mambalgin1 binds to the thumb domain of human ASIC1a channel and inhibits the channel through hindering the proton-induced transitions from the resting closed state to the active and/or desensitized state.
The rotation of the β11-12 linker is a crucial control point for acid-sensing ion channel gating and motion of this linker is required for the channel to desensitize.
The tarantula toxins psalmotoxin and guangxitoxin have a similar concave surface for interacting with α-helices in voltage-gated and acid-sensing ion channels.
Three residues work together as a valve-like mechanism to control desensitization from pre-open and open states in the ion channels ASIC1a, ASIC2a, and ASIC3.