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. 2022 Jun 3;13:908867. doi: 10.3389/fphar.2022.908867

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Copyright © 2022 Jiang, Zhang and Xia.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The ion path of mammalian Na_V channels. (A) The pore radii of human Na_V1.7 (PDB code: 7XM9) calculated by HOLE. Only two opposing subunits shown for clarity. The constriction sites of selectivity filter (SF) and intracellular activation gate (AG) are highlighted. (B) A close-up view of the SF (top panel) and AG (bottom panel) of human Na_V1.7 (PDB code: 7XM9). The SF of Na_V1.7 was aligned with the SF of Na_VAb (gray, PDB code: 3RVY). The side-chains of key residues in the SF and the AG are depicted in sticks. (C) The TTX binding site in Na_V1.7 (PDB code: 6J8I). The TTX-insensitive channel Na_V1.5 (PDB code: 6UZ3) shown in gray. (D) Fenestrations of human Na_V1.7 (PDB code: 7XM9). Red arrows indicate potential access for lipids or pore-blockers.