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However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB1 receptor knockdown (skmCB1-KD) mouse model using the Cre\/LoxP system. In this study, we aimed to clarify the mechanisms behind the observed reduction in muscle force generation in these mice. To investigate this, we analyzed calcium dynamics following electrical stimulation-induced muscle fatigue, assessed store-operated calcium entry (SOCE), and performed functional analysis of mitochondrial respiration. Our findings suggest that the reduced muscle performance observed in vivo likely arises from interconnected alterations in ATP production by mitochondria. Moreover, in skmCB1-KD mice, we detected a significant decrease in a component of the respiratory chain (complex IV) and a slowed dissipation of mitochondrial membrane potential upon the addition of an un-coupler (FCCP).<\/jats:p>","DOI":"10.3390\/ijms26115291","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Physiological Muscle Function Is Controlled by the Skeletal Endocannabinoid System in Murine Skeletal Muscles"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6949-0007","authenticated-orcid":false,"given":"Nyamkhuu","family":"Ganbat","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Singl\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-2282","authenticated-orcid":false,"given":"P\u00e9ter","family":"Szentesi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN Cell Physiology Research Group, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6346-4584","authenticated-orcid":false,"given":"Elena","family":"Lilliu","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8299-105X","authenticated-orcid":false,"given":"Zolt\u00e1n M\u00e1rton","family":"Kohler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Juh\u00e1sz","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-8458","authenticated-orcid":false,"given":"Anik\u00f3","family":"Keller-Pint\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2423-4966","authenticated-orcid":false,"given":"Xaver","family":"Koenig","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-8370","authenticated-orcid":false,"given":"Fabio Arturo","family":"Iannotti","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry (ICB), National Research Council of Italy (CNR), 80078 Pozzuoli, NA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-1456","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Csernoch","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN Cell Physiology Research Group, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5946-6986","authenticated-orcid":false,"given":"M\u00f3nika","family":"Sztretye","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN Cell Physiology Research Group, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/ajcn\/84.3.475","article-title":"The Underappreciated Role of Muscle in Health and Disease","volume":"84","author":"Wolfe","year":"2006","journal-title":"Am. 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