دورية أكاديمية
Role of cardiac mitofusins in cardiac conduction following simulated ischemia–reperfusion
العنوان: | Role of cardiac mitofusins in cardiac conduction following simulated ischemia–reperfusion |
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المؤلفون: | Xiu-Yi Kwek, Andrew R. Hall, Wei-Wen Lim, Khairunnisa Katwadi, Poh Loong Soong, Elina Grishina, Kun-Han Lin, Gustavo Crespo-Avilan, En Ping Yap, Nur Izzah Ismail, Kroekkiat Chinda, Ying Ying Chung, Heming Wei, Winston Shim, David Montaigne, Andrew Tinker, Sang-Bing Ong, Derek J. Hausenloy |
المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-13 (2022) |
بيانات النشر: | Nature Portfolio, 2022. |
سنة النشر: | 2022 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | Abstract Mitochondrial dysfunction induced by acute cardiac ischemia–reperfusion (IR), may increase susceptibility to arrhythmias by perturbing energetics, oxidative stress production and calcium homeostasis. Although changes in mitochondrial morphology are known to impact on mitochondrial function, their role in cardiac arrhythmogenesis is not known. To assess action potential duration (APD) in cardiomyocytes from the Mitofusins-1/2 (Mfn1/Mfn2)-double-knockout (Mfn-DKO) compared to wild-type (WT) mice, optical-electrophysiology was conducted. To measure conduction velocity (CV) in atrial and ventricular tissue from the Mfn-DKO and WT mice, at both baseline and following simulated acute IR, multi-electrode array (MEA) was employed. Intracellular localization of connexin-43 (Cx43) at baseline was evaluated by immunohistochemistry, while Cx-43 phosphorylation was assessed by Western-blotting. Mfn-DKO cardiomyocytes demonstrated an increased APD. At baseline, CV was significantly lower in the left ventricle of the Mfn-DKO mice. CV decreased with simulated-ischemia and returned to baseline levels during simulated-reperfusion in WT but not in atria of Mfn-DKO mice. Mfn-DKO hearts displayed increased Cx43 lateralization, although phosphorylation of Cx43 at Ser-368 did not differ. In summary, Mfn-DKO mice have increased APD and reduced CV at baseline and impaired alterations in CV following cardiac IR. These findings were associated with increased Cx43 lateralization, suggesting that the mitofusins may impact on post-MI cardiac-arrhythmogenesis. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2045-2322 |
Relation: | https://doaj.org/toc/2045-2322 |
DOI: | 10.1038/s41598-022-25625-0 |
URL الوصول: | https://doaj.org/article/e1c3d69e278a413bb5c1514faa5a9a65 |
رقم الأكسشن: | edsdoj.1c3d69e278a413bb5c1514faa5a9a65 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20452322 |
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DOI: | 10.1038/s41598-022-25625-0 |