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The role of activation of two different sGC binding sites by NO-dependent and NO-independent mechanisms in the regulation of SACs in rat ventricular cardiomyocytesстатья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 20 апреля 2022 г.
- Авторы: Kamkin Andre G., Kamkina Olga V., Shim Andrey L., Bilichenko Andrey, Mitrokhin Vadim M., Kazansky Viktor E., Filatova Tatiana S., Abramochkin Denis V., Mladenov Mitko I.
- Журнал: PHYSIOLOGICAL REPORTS
- Том: 10
- Номер: 7
- Год издания: 2022
- Первая страница: e15246
- DOI: 10.14814/phy2.15246
- Аннотация: The mechanoelectrical feedback (MEF) mechanism in the heart that plays a significant role in the occurrence of arrhythmias, involves cation flux through cation nonselective stretch-activated channels (SACs). It is well known that nitric oxide (NO) can act as a regulator of MEF. Here we addressed the possibility of SAC’s regulation along NO-dependent and NO-independent pathways, as well as the possibility of S-nitrosylation of SACs. In freshly isolated rat ventricular cardiomyocytes, using the patch-clamp method in whole-cell configuration, inward nonselective stretch-activated cation current ISAC was recorded through SACs, which occurs during dosed cell stretching. NO donor SNAP, α1-subunit of sGC activator BAY41-2272, sGC blocker ODQ, PKG blocker KT5823, PKG activator 8Br-cGMP, and S-nitrosylation blocker ascorbic acid, were employed. We concluded that the physiological concentration of NO in the cell is a necessary condition for the functioning of SACs. An increase in NO due to SNAP in an unstretched cell causes the appearance of a Gd3+-sensitive nonselective cation current, an analog of ISAC, while in a stretched cell it eliminates ISAC. The NO-independent pathway of sGC activation of α subunit, triggered by BAY41-2272, is also important for the regulation of SACs. Since S-nitrosylation inhibitor completely abolishes ISAC, this mechanism occurs. The application of BAY41-2272 cannot induce ISAC in a nonstretched cell; however, the addition of SNAP on its background activates SACs, rather due to S-nitrosylation.ODQ eliminates ISAC, but SNAP added on the background of stretch increases ISAC 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 SACs phosphorylation, leading to an increase in ISAC. 8Br-cGMP reduces ISAC by activating PKG and its phosphorylation. These results demonstrate a significant contribution of S-nitrosylation to the regulation of SACs.
- Добавил в систему: Филатова Татьяна Сергеевна