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Updated: Jul 12, 2026

Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors
Published on: February 10, 2014
Barium senses subtle pore changes in a voltage-gated K+ channel associated with voltage sensor states and regulatory
Lei Huang1, Nitzan Daus2, Yuyin Wang1
1Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St. Louis, MO 63130, USA.
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.
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