Academic Journal
Ablation of Calsequestrin-1, Ca2+ unbalance, and susceptibility to heat stroke
| العنوان: | Ablation of Calsequestrin-1, Ca2+ unbalance, and susceptibility to heat stroke |
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| المؤلفون: | Protasi, F., Girolami, B., Serano, M., Pietrangelo, L., Paolini, C. |
| المساهمون: | Protasi, F., Girolami, B., Serano, M., Pietrangelo, L., Paolini, C. |
| سنة النشر: | 2022 |
| المجموعة: | Università degli Studi di Siena: USiena air |
| مصطلحات موضوعية: | Ca, 2+, entry unit (CEU), calsequestrin (Casq), excitation-contraction (EC) coupling, malignant hyperthermia susceptibility (MHS), ryanodine receptor (RyR), store-operated Ca, entry (SOCE) |
| الوصف: | Introduction: Ca2+ levels in adult skeletal muscle fibers are mainly controlled by excitation-contraction (EC) coupling, a mechanism that translates action potentials in release of Ca2+ from the sarcoplasmic reticulum (SR) release channels, i.e. the ryanodine receptors type-1 (RyR1). Calsequestrin (Casq) is a protein that binds large amounts of Ca2+ in the lumen of the SR terminal cisternae, near sites of Ca2+ release. There is general agreement that Casq is not only important for the SR ability to store Ca2+, but also for modulating the opening probability of the RyR Ca2+ release channels. The initial studies: About 20years ago we generated a mouse model lacking Casq1 (Casq1-null mice), the isoform predominantly expressed in adult fast twitch skeletal muscle. While the knockout was not lethal as expected, lack of Casq1 caused a striking remodeling of membranes of SR and of transverse tubules (TTs), and mitochondrial damage. Functionally, CASQ1-knockout resulted in reduced SR Ca2+ content, smaller Ca2+ transients, and severe SR depletion during repetitive stimulation. The myopathic phenotype of Casq1-null mice: After the initial studies, we discovered that Casq1-null mice were prone to sudden death when exposed to halogenated anaesthetics, heat and even strenuous exercise. These syndromes are similar to human malignant hyperthermia susceptibility (MHS) and environmental-exertional heat stroke (HS). We learned that mechanisms underlying these syndromes involved excessive SR Ca2+ leak and excessive production of oxidative species: indeed, mortality and mitochondrial damage were significantly prevented by administration of antioxidants and reduction of oxidative stress. Though, how Casq1-null mice could survive without the most important SR Ca2+ binding protein was a puzzling issue that was not solved. Unravelling the mystery: The mystery was finally solved in 2020, when we discovered that in Casq1-null mice the SR undergoes adaptations that result in constitutively active store-operated Ca2+ entry (SOCE). SOCE is ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/36311237; info:eu-repo/semantics/altIdentifier/wos/WOS:000876950500001; volume:13; numberofpages:16; journal:FRONTIERS IN PHYSIOLOGY; https://hdl.handle.net/11365/1227900; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85140579949; https://www.frontiersin.org/articles/10.3389/fphys.2022.1033300/full |
| DOI: | 10.3389/fphys.2022.1033300 |
| DOI: | 10.3389/fphys.2022.1033300/full |
| الاتاحة: | https://hdl.handle.net/11365/1227900 https://doi.org/10.3389/fphys.2022.1033300 https://www.frontiersin.org/articles/10.3389/fphys.2022.1033300/full |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.33160044 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fphys.2022.1033300 |
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