Please wait, while we are loading the content...
Please wait, while we are loading the content...
| Content Provider | frontiers |
|---|---|
| Author | Protasi, Feliciano Girolami, Barbara Serano, Matteo Pietrangelo, Laura Paolini, Cecilia |
| Abstract | 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. 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 twenty years ago we generated a mouse model lacking isoform 1 of CASQ (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 the SR and of transverse-tubule (TT) membranes, and mitochondrial damage. Functionally, CASQ1-knockout resulted in reduced SR Ca2+ content and release, and severe SR depletion during repetitive stimulation. The myopathic phenotype of CASQ1-null mice. After the initial studies, though, 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 the syndrome 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 yet was not solved. Unravelling the mystery. The mystery was finally solved in 2020, when we discovered that in CASQ1-null mice the SR activates a compensatory mechanism that results in constitutively active store-operated Ca2+ entry (SOCE), a mechanism that allows skeletal fibers to use external Ca2+ when SR stores are depleted. The post-natal compensatory mechanism that allows CASQ1-null mice to survive involves the assembly of new SR-TT junctions (Ca2+ entry units) containing STIM1 and ORAI1, the two proteins that mediate SOCE. |
| ISSN | 1664042X |
| DOI | 10.3389/fphys.2022.1033300 |
| Volume Number | 13 |
| Journal | Frontiers in Physiology |
| Language | English |
| Publisher Date | 2022-10-12 |
| Access Restriction | Open |
| Subject Keyword | Ca2+ entry unit (CEU) Excitation-contraction (EC) coupling Malignant hyperthermia susceptibility (MHS) Store-operated Ca2+ entry (SOCE) Ryanodine receptor (RyR) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) |
National Digital Library of India (NDLI) is a virtual repository of learning resources which is not just a repository with search/browse facilities but provides a host of services for the learner community. It is sponsored and mentored by Ministry of Education, Government of India, through its National Mission on Education through Information and Communication Technology (NMEICT). Filtered and federated searching is employed to facilitate focused searching so that learners can find the right resource with least effort and in minimum time. NDLI provides user group-specific services such as Examination Preparatory for School and College students and job aspirants. Services for Researchers and general learners are also provided. NDLI is designed to hold content of any language and provides interface support for 10 most widely used Indian languages. It is built to provide support for all academic levels including researchers and life-long learners, all disciplines, all popular forms of access devices and differently-abled learners. It is designed to enable people to learn and prepare from best practices from all over the world and to facilitate researchers to perform inter-linked exploration from multiple sources. It is developed, operated and maintained from Indian Institute of Technology Kharagpur.
Learn more about this project from here.
NDLI is a conglomeration of freely available or institutionally contributed or donated or publisher managed contents. Almost all these contents are hosted and accessed from respective sources. The responsibility for authenticity, relevance, completeness, accuracy, reliability and suitability of these contents rests with the respective organization and NDLI has no responsibility or liability for these. Every effort is made to keep the NDLI portal up and running smoothly unless there are some unavoidable technical issues.
Ministry of Education, through its National Mission on Education through Information and Communication Technology (NMEICT), has sponsored and funded the National Digital Library of India (NDLI) project.
| Sl. | Authority | Responsibilities | Communication Details |
|---|---|---|---|
| 1 | Ministry of Education (GoI), Department of Higher Education |
Sanctioning Authority | https://www.education.gov.in/ict-initiatives |
| 2 | Indian Institute of Technology Kharagpur | Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project | https://www.iitkgp.ac.in |
| 3 | National Digital Library of India Office, Indian Institute of Technology Kharagpur | The administrative and infrastructural headquarters of the project | Dr. B. Sutradhar bsutra@ndl.gov.in |
| 4 | Project PI / Joint PI | Principal Investigator and Joint Principal Investigators of the project |
Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon |
| 5 | Website/Portal (Helpdesk) | Queries regarding NDLI and its services | support@ndl.gov.in |
| 6 | Contents and Copyright Issues | Queries related to content curation and copyright issues | content@ndl.gov.in |
| 7 | National Digital Library of India Club (NDLI Club) | Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach | clubsupport@ndl.gov.in |
| 8 | Digital Preservation Centre (DPC) | Assistance with digitizing and archiving copyright-free printed books | dpc@ndl.gov.in |
| 9 | IDR Setup or Support | Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops | idr@ndl.gov.in |
|
Loading...
|