Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1

Abstract Hydrogen sulfide (H2S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H2S acts. Ion channels and neuronal receptors are key target proteins for S-sulfh...

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Autores principales:	Mark L. Dallas, Moza M. Al-Owais, Nishani T. Hettiarachchi, Matthew Scott Vandiver, Heledd H. Jarosz-Griffiths, Jason L. Scragg, John P. Boyle, Derek Steele, Chris Peers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13083c3f35814e67b0e44923d6daf923
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spelling	oai:doaj.org-article:13083c3f35814e67b0e44923d6daf9232021-12-02T14:27:53ZHydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.110.1038/s41598-021-87646-52045-2322https://doaj.org/article/13083c3f35814e67b0e44923d6daf9232021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87646-5https://doaj.org/toc/2045-2322Abstract Hydrogen sulfide (H2S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H2S acts. Ion channels and neuronal receptors are key target proteins for S-sulfhydration and this can influence a range of neuronal functions. Voltage-gated K+ channels, including Kv2.1, are fundamental components of neuronal excitability. Here, we show that both recombinant and native rat Kv2.1 channels are inhibited by the H2S donors, NaHS and GYY4137. Biochemical investigations revealed that NaHS treatment leads to S-sulfhydration of the full length wild type Kv2.1 protein which was absent (as was functional regulation by H2S) in the C73A mutant form of the channel. Functional experiments utilising primary rat hippocampal neurons indicated that NaHS augments action potential firing and thereby increases neuronal excitability. These studies highlight an important role for H2S in shaping cellular excitability through S-sulfhydration of Kv2.1 at C73 within the central nervous system.Mark L. DallasMoza M. Al-OwaisNishani T. HettiarachchiMatthew Scott VandiverHeledd H. Jarosz-GriffithsJason L. ScraggJohn P. BoyleDerek SteeleChris PeersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mark L. Dallas Moza M. Al-Owais Nishani T. Hettiarachchi Matthew Scott Vandiver Heledd H. Jarosz-Griffiths Jason L. Scragg John P. Boyle Derek Steele Chris Peers Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
description	Abstract Hydrogen sulfide (H2S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H2S acts. Ion channels and neuronal receptors are key target proteins for S-sulfhydration and this can influence a range of neuronal functions. Voltage-gated K+ channels, including Kv2.1, are fundamental components of neuronal excitability. Here, we show that both recombinant and native rat Kv2.1 channels are inhibited by the H2S donors, NaHS and GYY4137. Biochemical investigations revealed that NaHS treatment leads to S-sulfhydration of the full length wild type Kv2.1 protein which was absent (as was functional regulation by H2S) in the C73A mutant form of the channel. Functional experiments utilising primary rat hippocampal neurons indicated that NaHS augments action potential firing and thereby increases neuronal excitability. These studies highlight an important role for H2S in shaping cellular excitability through S-sulfhydration of Kv2.1 at C73 within the central nervous system.
format	article
author	Mark L. Dallas Moza M. Al-Owais Nishani T. Hettiarachchi Matthew Scott Vandiver Heledd H. Jarosz-Griffiths Jason L. Scragg John P. Boyle Derek Steele Chris Peers
author_facet	Mark L. Dallas Moza M. Al-Owais Nishani T. Hettiarachchi Matthew Scott Vandiver Heledd H. Jarosz-Griffiths Jason L. Scragg John P. Boyle Derek Steele Chris Peers
author_sort	Mark L. Dallas
title	Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
title_short	Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
title_full	Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
title_fullStr	Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
title_full_unstemmed	Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
title_sort	hydrogen sulfide regulates hippocampal neuron excitability via s-sulfhydration of kv2.1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/13083c3f35814e67b0e44923d6daf923
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Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1

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