Canna~Fangled Abstracts

Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres.

By June 24, 2015 No Comments
 2015 Jun 24. doi: 10.1113/JP270522. [Epub ahead of print]


PM 1aIncreased 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 Ca2+ from intracellular pools. We observed that both hyperosmotic shock-induced Ca2+ transients and RVI were inhibited by Gd3+ , 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 Ca2+ 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 Ca2+ 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 Ca2+ transients were abolished by the Ca2+ chelator BAPTA, the level of P-SPAKSer373 in response to hyperosmotic shock was reduced, suggesting a modulation of SPAK phosphorylation by intracellular Ca2+ . 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.
This article is protected by copyright. All rights reserved.

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