Potential salt bridge between R63 _hASIC3 and E430 _hASIC3 . (A) Top-down view of the transmembrane domain of a structure of the cASIC1 resting state (PDB: 5WKU) shown as cyan cartoon. Conserved residues R65_cASICa and E413_cASIC1 are shown as sticks. (B) The same representation as A, however, of the open state structure of cASIC1 (PDB: 4NTW). A change in the position of R65_cASIC1 and E413_cASIC1 suggests a breaking of this salt bridge in the open state of the channel upon rotation and opening of the TM helices. (C) Position of residues R63_hASIC3 and E430_hASIC3 sampled in one atomistic simulation of the resting hASIC3 state. (D) Position of residues R63_hASIC3 and E430_hASIC3 sampled in one atomistic simulation of the open hASIC3 state.