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In this study, we examine its regulation by hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) 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 H<jats:sub>2<\/jats:sub>S producing enzymes protein expression in HL-1 cardiomyocytes. H<jats:sub>2<\/jats:sub>S supplementation reduced these remodeling changes and restored action potential duration through inhibition of Kv1.5 channel. H<jats:sub>2<\/jats:sub>S 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 I<jats:sub>kur<\/jats:sub> by H<jats:sub>2<\/jats:sub>S has important cardiovascular implications and represents a novel and potential therapeutic target.<\/jats:p>","DOI":"10.1038\/s42003-023-05016-5","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T14:02:33Z","timestamp":1687183353000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of the voltage-gated potassium channel Kv1.5 by hydrogen sulfide attenuates remodeling through S-nitrosylation-mediated signaling"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9122-7873","authenticated-orcid":false,"given":"Moza M.","family":"Al-Owais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishani T.","family":"Hettiarachchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-0522","authenticated-orcid":false,"given":"Mark L.","family":"Dallas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Scragg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-7345","authenticated-orcid":false,"given":"Jonathan D.","family":"Lippiat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-2561","authenticated-orcid":false,"given":"Arun V.","family":"Holden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek S.","family":"Steele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Peers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,19]]},"reference":[{"key":"5016_CR1","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.jtbi.2008.06.030","volume":"254","author":"EM Cherry","year":"2008","unstructured":"Cherry, E. 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