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Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres
| Content Provider | Scilit |
|---|---|
| Author | Zanou, Nadège Mondin, Ludivine Fuster, Clarisse Seghers, François Dufour, Inès de Clippele, Marie Schakman, Olivier Tajeddine, Nicolas Iwata, Yuko Wakabayashi, Shigeo Voets, Thomas Allard, Bruno Gailly, Philippe |
| Copyright Year | 2015 |
| Description | Journal: The Journal of physiology |
| Abstract | Increased plasma osmolarity induces intracellular water depletion and cell shrinkage (CS) followed by activation of a regulatory volume increase (RVI). In skeletal muscle, the hyperosmotic shock-induced CS is accompanied by a small membrane depolarization responsible for a release of Ca(2+) from intracellular pools. Hyperosmotic shock also induces phosphorylation of STE20/SPS1-related proline/alanine-rich kinase (SPAK). TRPV2 dominant negative expressing fibres challenged with hyperosmotic shock present a slower membrane depolarization, a diminished Ca(2+) response, a smaller RVI response, a decrease in SPAK phosphorylation and defective muscle function. We suggest that hyperosmotic shock induces TRPV2 activation, which accelerates muscle cell depolarization and allows the subsequent Ca(2+) release from the sarcoplasmic reticulum, activation of the Na(+) -K(+) -Cl(-) cotransporter by SPAK, and the RVI response. Increased plasma osmolarity induces intracellular water depletion and cell shrinkage followed by activation of a regulatory volume increase (RVI). In skeletal muscle, this is accompanied by transverse tubule (TT) dilatation and by a membrane depolarization responsible for a release of Ca(2+) from intracellular pools. We observed that both hyperosmotic shock-induced Ca(2+) transients and RVI were inhibited by Gd(3+) , ruthenium red and GsMTx4 toxin, three inhibitors of mechanosensitive ion channels. The response was also completely absent in muscle fibres overexpressing a non-permeant, dominant negative (DN) mutant of the transient receptor potential, V2 isoform (TRPV2) ion channel, suggesting the involvement of TRPV2 or of a TRP isoform susceptible to heterotetramerization with TRPV2. The release of Ca(2+) induced by hyperosmotic shock was increased by cannabidiol, an activator of TRPV2, and decreased by tranilast, an inhibitor of TRPV2, suggesting a role for the TRPV2 channel itself. Hyperosmotic shock-induced membrane depolarization was impaired in TRPV2-DN fibres, suggesting that TRPV2 activation triggers the release of Ca(2+) from the sarcoplasmic reticulum by depolarizing TTs. RVI requires the sequential activation of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NKCC1, a Na(+) -K(+) -Cl(-) cotransporter, allowing ion entry and driving osmotic water flow. In fibres overexpressing TRPV2-DN as well as in fibres in which Ca(2+) transients were abolished by the Ca(2+) chelator BAPTA, the level of P-SPAK(Ser373) in response to hyperosmotic shock was reduced, suggesting a modulation of SPAK phosphorylation by intracellular Ca(2+) . We conclude that TRPV2 is involved in osmosensation in skeletal muscle fibres, acting in concert with P-SPAK-activated NKCC1. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575573/pdf |
| Ending Page | 3863 |
| Page Count | 15 |
| Starting Page | 3849 |
| ISSN | 00223751 |
| e-ISSN | 14697793 |
| DOI | 10.1113/jp270522 |
| Journal | The Journal of physiology |
| Issue Number | 17 |
| Volume Number | 593 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2015-08-10 |
| Access Restriction | Open |
| Subject Keyword | Journal: The Journal of physiology Proline/alanine Rich Kinase Ste20/sps1 Related Proline/alanine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
