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It is well known that nitric oxide (NO) can act as a regulator of MEF. Here we addressed the possibility of <jats:italic>SAC\u2019s<\/jats:italic> regulation along NO\u2010dependent and NO\u2010independent pathways, as well as the possibility of S\u2010nitrosylation of <jats:italic>SACs<\/jats:italic>. In freshly isolated rat ventricular cardiomyocytes, using the patch\u2010clamp method in whole\u2010cell configuration, inward nonselective stretch\u2010activated cation current <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic> was recorded through <jats:italic>SACs<\/jats:italic>, which occurs during dosed cell stretching. NO donor SNAP, \u03b11\u2010subunit of sGC activator BAY41\u20102272, sGC blocker ODQ, PKG blocker KT5823, PKG activator 8Br\u2010cGMP, and S\u2010nitrosylation blocker ascorbic acid, were employed. We concluded that the physiological concentration of NO in the cell is a necessary condition for the functioning of <jats:italic>SACs<\/jats:italic>. An increase in NO due to SNAP in an unstretched cell causes the appearance of a Gd<jats:sup>3+<\/jats:sup>\u2010sensitive nonselective cation current, an analog of <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic>, while in a stretched cell it eliminates <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic>. The NO\u2010independent pathway of sGC activation of <jats:italic>\u03b1<\/jats:italic> subunit, triggered by BAY41\u20102272, is also important for the regulation of <jats:italic>SACs<\/jats:italic>. Since S\u2010nitrosylation inhibitor completely abolishes <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic>, this mechanism occurs. The application of BAY41\u20102272 cannot induce <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic> in a nonstretched cell; however, the addition of SNAP on its background activates <jats:italic>SACs<\/jats:italic>, rather due to S\u2010nitrosylation.<\/jats:p><jats:p>ODQ eliminates <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic>, but SNAP added on the background of stretch increases <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic> in addition to ODQ. This may be a result of the lack of NO as a result of inhibition of NOS by metabolically modified ODQ. KT5823 reduces PKG activity and reduces <jats:italic>SACs<\/jats:italic> phosphorylation, leading to an increase in <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic>. 8Br\u2010cGMP reduces <jats:italic>I<jats:sub>SAC<\/jats:sub><\/jats:italic> by activating PKG and its phosphorylation. These results demonstrate a significant contribution of S\u2010nitrosylation to the regulation of <jats:italic>SACs<\/jats:italic>.<\/jats:p>","DOI":"10.14814\/phy2.15246","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T14:04:07Z","timestamp":1649167447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The role of activation of two different sGC binding sites by NO\u2010dependent and NO\u2010independent mechanisms in the regulation of <i>SACs<\/i> in rat ventricular cardiomyocytes"],"prefix":"10.14814","volume":"10","author":[{"given":"Andre G.","family":"Kamkin","sequence":"first","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Kamkina","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey L.","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Bilichenko","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim M.","family":"Mitrokhin","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor E.","family":"Kazansky","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana S.","family":"Filatova","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"},{"name":"Department of Human and Animal Physiology Lomonosov Moscow State University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis\u00a0V.","family":"Abramochkin","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"},{"name":"Department of Human and Animal Physiology Lomonosov Moscow State University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-2131","authenticated-orcid":false,"given":"Mitko I.","family":"Mladenov","sequence":"additional","affiliation":[{"name":"Department of Physiology Pirogov Russian National Research Medical University  Moscow Russia"},{"name":"Faculty of Natural Sciences and Mathematics Institute of Biology, \u201cSs. 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