Extracellular redox sensitivity of Kv1.2 potassium channels

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 unkn...

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Autores principales:	Victoria A. Baronas, Runying Y. Yang, Harley T. Kurata
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2edbcc92d694f99843b6c64597596bb
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spelling	oai:doaj.org-article:b2edbcc92d694f99843b6c64597596bb2021-12-02T16:06:31ZExtracellular redox sensitivity of Kv1.2 potassium channels10.1038/s41598-017-08718-z2045-2322https://doaj.org/article/b2edbcc92d694f99843b6c64597596bb2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08718-zhttps://doaj.org/toc/2045-2322Abstract 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.Victoria A. BaronasRunying Y. YangHarley T. KurataNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Victoria A. Baronas Runying Y. Yang Harley T. Kurata Extracellular redox sensitivity of Kv1.2 potassium channels
description	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.
format	article
author	Victoria A. Baronas Runying Y. Yang Harley T. Kurata
author_facet	Victoria A. Baronas Runying Y. Yang Harley T. Kurata
author_sort	Victoria A. Baronas
title	Extracellular redox sensitivity of Kv1.2 potassium channels
title_short	Extracellular redox sensitivity of Kv1.2 potassium channels
title_full	Extracellular redox sensitivity of Kv1.2 potassium channels
title_fullStr	Extracellular redox sensitivity of Kv1.2 potassium channels
title_full_unstemmed	Extracellular redox sensitivity of Kv1.2 potassium channels
title_sort	extracellular redox sensitivity of kv1.2 potassium channels
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b2edbcc92d694f99843b6c64597596bb
work_keys_str_mv	AT victoriaabaronas extracellularredoxsensitivityofkv12potassiumchannels AT runyingyyang extracellularredoxsensitivityofkv12potassiumchannels AT harleytkurata extracellularredoxsensitivityofkv12potassiumchannels
_version_	1718384983859527680

Extracellular redox sensitivity of Kv1.2 potassium channels

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