Extracellular redox sensitivity of Kv1.2 potassium channels

Victoria A Baronas,Runying Y Yang,Harley T Kurata

doi:10.1038/s41598-017-08718-z

Victoria A Baronas, Runying Y Yang + Show 1 more

Open Access

https://doi.org/10.1038/s41598-017-08718-z

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Journal: Scientific Reports	Publication Date: Aug 22, 2017
Citations: 20	License type: open-access

Affiliation: University of Alberta

Abstract

Kv1.2 is a prominent potassium channel subtype in the nervous system and serves as an important structural template for investigation of ion channel function. However, Kv1.2 voltage-dependence exhibits dramatic cell-to-cell variability due to a gating mode shift that is regulated by an unknown mechanism. We report that this variable behavior is regulated by the extracellular redox environment. Exposure to reducing agents promotes a shift in gating properties towards an ‘inhibited’ gating mode that resists opening, and causes channels to exhibit pronounced use-dependent activation during trains of repetitive depolarizations. This sensitivity to extracellular redox potential is absent in other Kv1 channels, but is apparent in heteromeric channels containing Kv1.2 subunits, and overlaps with the reported physiological range of extracellular redox couples. Mutagenesis of candidate cysteine residues fails to abolish redox sensitivity. Therefore, we suggest that an extrinsic, redox-sensitive binding partner imparts these properties.

Highlights

Kv1.2 is a voltage-gated potassium channel subtype that is most prominently expressed in the central nervous system, where it assembles with other members of the Kv1 channel subfamily, auxiliary β-subunits, and potentially other interacting partners that may regulate expression and function[1,2,3]
We have recently reported a detailed description of the cell-to-cell variability of Kv1.2 regulation, by characterizing its property of ‘use-dependent activation’[5, 10]
This is true of Kv1.2, which assembles in heterotetrameric complexes with other Kv1 channels, and can recruit sensitivity to use-dependent activation[5]

Summary

Introduction

Kv1.2 is a voltage-gated potassium channel subtype that is most prominently expressed in the central nervous system, where it assembles with other members of the Kv1 channel subfamily, auxiliary β-subunits, and potentially other interacting partners that may regulate expression and function[1,2,3]. Exposure of Kv1.2 to reducing conditions causes these channels to exhibit pronounced use-dependent activation as channels ‘escape’ from the inhibited gating mode upon membrane depolarization. We observed that cells expressing Kv1.2 channels exhibit a wide range of V1/2 of activation, from −1.7 mV to +43 mV, illustrated by data collected from individual cells (Fig. 1A, gray lines).

Results

Conclusion