Predicted structures of hASIC1a mutants in the open conformation exhibit enlarged pore radii and altered interaction networks in the lower pore. (A) Right: Pore radius profile of WT hASIC1a compared with nonselective mutants. Left: Pore radius profile of WT hASIC1a compared with selective mutants using HOLE2 software. (B) Bottom view of R28^hASIC1a ion pore in the predicted open conformation, highlighting the architecture and sizes of the rings defined by the GAS belt and R28 in the reentrant loop. (C) Side view of the ion permeation pathway of predicted R28^hASIC1a in the open conformation (left panel) and an enlarged view of the ion permeation pathway with residues in stick representation lining the ion pathway: G444, R28, T26, S25, S24, and S23 (right panel). (D) Side view of predicted R28^hASIC1a pore in the open conformation (left panel) highlights altered interaction networks formed by residues R28, T26, and the lower pore (right panel). Three TM1 helices (deep teal/cyan/pale cyan), two TM2 helices (cyan/pale cyan), and reentrant loops (violet/light pink) are shown for simplicity.