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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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Putative models for modulation of VSDs of Na_V channels. (A) Activation of VSD_I and VSD_II cause channel opening. Green balls represent sodium ions. Red arrow indicates activation of the VSD. (B) Site-4 toxin HwTx-IV traps VSD_II in a deactivated state and inhibits channel opening. Green arrow indicates deactivation of the VSD. (C) α-Scorpion toxin LqhIII traps VSD_IV in a deactivated state and inhibits fast inactivation. (D) Aryl sulfonamide analogue ICA121431 binds to activated VSD_IV and inhibits channel opening.