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. 2023 Nov 18;14:7515. doi: 10.1038/s41467-023-43280-5

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — a Activation diagram for AtHv1 shows that the channel is locked in a stabilized resting-closed conformation (RC_S silent state) which prevents channel opening. Mechanical priming destabilizes the resting-closed conformation (transition to RC) allowing the VSD to reach the activated open conformation. b Schematics of changes proposed for the RC_S → RC transition, which include the destabilization of the RSN in the inner vestibule (upper panel) and a disengagement of K154 from the membrane surface (lower panel). In addition, S164 could move closer to the first S4 arginine (black arrow) interfering with its electrostatic interaction with D75. The result of these changes is expected to make it easier for S4 to reach the activated conformation upon membrane depolarization. c Activation diagram for PsHv1 showing that the channel is in a state similar to the mechanically-primed resting state of AtHv1 (RC) even in the absence of a mechanical stimulus. d Reaction coordinate diagram for the process of channel activation showing the proposed change in energy profile induced by mechanical priming. Intermediate states preceding the activated state have been omitted for simplicity.