Ryanodine receptor leak triggers fiber Ca2+ redistribution to preserve force and elevate basal metabolism in skeletal muscle
| العنوان: | Ryanodine receptor leak triggers fiber Ca2+ redistribution to preserve force and elevate basal metabolism in skeletal muscle |
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| المؤلفون: | Robyn M. Murphy, Barnaby P. Frankish, Bradley S. Launikonis, Harriet P. Lo, Paul D. Allen, Aldo Meizoso-Huesca, Luke Pearce, Cedric R. Lamboley, Chris van der Poel, Charles Ferguson, Robert G. Parton, Crystal Seng, Christopher John Barclay, Vikas Kaura, Daniel P. Singh, Philip M. Hopkins |
| المصدر: | Science Advances |
| بيانات النشر: | La Trobe, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | RYR1, Leak, Multidisciplinary, Physiology, Chemistry, Ryanodine receptor, Endoplasmic reticulum, Biophysics, SciAdv r-articles, Skeletal muscle, Heatstroke, medicine.disease, musculoskeletal system, Cell biology, medicine.anatomical_structure, Basal metabolic rate, medicine, Biomedicine and Life Sciences, medicine.symptom, tissues, Research Article, Muscle contraction, Uncategorized |
| الوصف: | Description RyR1 Ca2+ leak causes a cascade of events that shifts Ca2+ to the cytoplasm and mitochondria, supporting force generation. Muscle contraction depends on tightly regulated Ca2+ release. Aberrant Ca2+ leak through ryanodine receptor 1 (RyR1) on the sarcoplasmic reticulum (SR) membrane can lead to heatstroke and malignant hyperthermia (MH) susceptibility, as well as severe myopathy. However, the mechanism by which Ca2+ leak drives these pathologies is unknown. Here, we investigate the effects of four mouse genotypes with increasingly severe RyR1 leak in skeletal muscle fibers. We find that RyR1 Ca2+ leak initiates a cascade of events that cause precise redistribution of Ca2+ among the SR, cytoplasm, and mitochondria through altering the Ca2+ permeability of the transverse tubular system membrane. This redistribution of Ca2+ allows mice with moderate RyR1 leak to maintain normal function; however, severe RyR1 leak with RYR1 mutations reduces the capacity to generate force. Our results reveal the mechanism underlying force preservation, increased ATP metabolism, and susceptibility to MH in individuals with gain-of-function RYR1 mutations. |
| DOI: | 10.26181/6196ee582c804 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f23394ad8035d2256dda06c6eae76be |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1f23394ad8035d2256dda06c6eae76be |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.26181/6196ee582c804 |
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