Barium senses subtle pore changes in a voltage-gated K⁺ channel associated with voltage sensor states and regulatory subunits.

Authors

Lei Huang, Nitzan Daus, Yuyin Wang, Guohui Zhang, Manar Khier, Ariel Ben-Bassat, Jingyi Shi, Lu Zhao, Borui Zhang, Lu Han, Yoni Haitin, Bernard Attali, Jianmin Cui

Published in

Science advances. Volume 12. Issue 28. Pages eaec6510. Jul 10, 2026. Epub Jul 10, 2026.

Abstract

In classic models of voltage-dependent channel activation, the pore only opens after the voltage sensor domains (VSDs) activate in an "all-or-none" fashion. Whether the VSD alters open pore properties remains unclear. Here, we examine the properties of the KCNQ1 channel pore in relation with the VSD and regulatory subunits that are located outside of the pore using barium ion (Ba²⁺) block as a probe. We find that the external Ba²⁺ block of KCNQ1 channels is voltage-dependent, and the voltage-dependent channel opening in Ba²⁺ mainly derives from voltage-dependent Ba²⁺ unblock. Open pore conformational changes indicated by the voltage dependence of Ba²⁺ unblock vary with the states of the VSD, the alterations of VSD-pore coupling, and the association with regulatory KCNE subunits. Contrary to the classic view, our results suggest that, instead of being independent of the voltage gating machinery, the pore of KCNQ1 is flexible and influenced by the subtle changes in the voltage sensor state and the environment outside of the pore.

PMID:
42430481
Bibliographic data and abstract were imported from PubMed on 11 Jul 2026.

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