Al-Owais, M orcid.org/0000-0001-9122-7873, Hettiarachchi, NT, Dallas, ML et al. (5 more authors) (2023) Inhibition of the voltage-gated potassium channel Kv1.5 by hydrogen sulfide attenuates remodeling through S-nitrosylation-mediated signaling. Communications Biology, 6. 651. ISSN 2399-3642
Abstract
The voltage-gated K⁺ channel plays a key role in atrial excitability, conducting the ultra-rapid rectifier K⁺ current (IKur) and contributing to the repolarization of the atrial action potential. In this study, we examine its regulation by hydrogen sulfide (H₂S) in HL-1 cardiomyocytes and in HEK293 cells expressing human Kv1.5. Pacing induced remodeling resulted in shorting action potential duration, enhanced both Kv1.5 channel and H₂S producing enzymes protein expression in HL-1 cardiomyocytes. H₂S supplementation reduced these remodeling changes and restored action potential duration through inhibition of Kv1.5 channel. H₂S also inhibited recombinant hKv1.5, lead to nitric oxide (NO) mediated S-nitrosylation and activated endothelial nitric oxide synthase (eNOS) by increased phosphorylation of Ser1177, prevention of NO formation precluded these effects. Regulation of Ikur by H₂S has important cardiovascular implications and represents a novel and potential therapeutic target.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number Heart Research UK RG2663/17/19 |
Depositing User: | Symplectic Publications |
Date Deposited: | 29 Jun 2023 15:00 |
Last Modified: | 29 Jun 2023 15:00 |
Status: | Published |
Publisher: | Nature |
Identification Number: | 10.1038/s42003-023-05016-5 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:200732 |