Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres.
(2015) The Journal of Physiology — Vol. 593, n° 17, p. 3849-3863 (2015)
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- 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) dilation and by a membrane depolarisation responsible of 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 mutant of TRPV2 ion channel (TRPV2-DN), suggesting the involvement of TRPV2 (Transient Receptor Potential, V2 isoform) or of a TRP isoform susceptible to heterotetramerize 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 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 TT. RVI requires the sequential activation of SPAK (STE20/SPS1-related proline/alanine-rich kinase) and NKCC1, a Na(+) , K(+) and Cl(-) cotransporter allowing ions entry and osmotic water driving. 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. This article is protected by copyright. All rights reserved.
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Zanou, B. N., Mondin, L., Fuster, C., Seghers, F., Dufour, I., De Clippele, M., Schakman, O., Tajeddine, N., Iwata, Y., Wakabayashi, S., Voets, T., Allard, B., & Gailly, P. (2015). Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres. The Journal of Physiology, 593(17), 3849-3863. https://doi.org/10.1113/JP270522 (Original work published 2015)