Predicted structure of the open pore of hASIC1a and radius of the ion permeation pathway. (A) Side view of the ion permeation pathway in the predicted open conformation of hASIC1a (left panel). Only two subunits are shown for clarity. The ion pathway is demarcated by purple dots. The TM domains are colored teal, and the reentrant loops are pink. An enlarged side view with residues lining the permeation pathway shows the following in sticks: G444, H28, T26, S25, S24, and S23 (right panel). (B) Side view illustration of the electrostatic potential distribution of the predicted hASIC1a open state model. Only two ASIC1 subunits and only the TM domains and the N-terminal reentrant loop are presented to visualize the interior surface of the central ion permeation pathway, which is demarcated by yellow dots. The coulombic electrostatic potential (ESP) was calculated by the built-in coulombic command in the UCSF Chimera system, with default coloring ranging from red for negative potential through white to blue for positive potential. (C) View from the cytosol of the ion pore in the predicted hASIC1a open conformation highlights the architecture and organization of the GAS belt of TM2 and the HG motif of the reentrant loop. (D) Profile of pore radius calculated by the HOLE2 program (Smart et al., 1996). hA_resting (7cfs), cryo-EM structure of hASIC1a at pH 8.0 (PDB accession no. 7CFS; Sun et al., 2020); hA_resting, predicted hASIC1a in the resting state; hA_open, predicted hASIC1a in the open conformation.