title: Characterization of functional TRPV1 channels in the sarcoplasmic reticulum of mouse skeletal muscle.
abstract: TRPV1 represents a non-selective cation channel activated by capsaicin, acidosis and high temperature. In the central nervous system where TRPV1 is highly expressed, its physiological role in nociception is clearly identified. In skeletal muscle, TRPV1 appears implicated in energy metabolism and exercise endurance. However, how as a Ca(2+) channel, it contributes to intracellular calcium concentration ([Ca(2+)]i) maintenance and muscle contraction remains unknown. Here, as in rats, we report that TRPV1 is functionally expressed in mouse skeletal muscle. In contrast to earlier reports, our analysis show TRPV1 presence only at the sarcoplasmic reticulum (SR) membrane (preferably at the longitudinal part) in the proximity of SERCA1 pumps. Using intracellular Ca(2+) imaging, we directly accessed to the channel functionality in intact FDB mouse fibers. Capsaicin and resiniferatoxin, both agonists as well as high temperature (45°C) elicited an increase in [Ca(2+)]i. TRPV1-inhibition by capsazepine resulted in a strong inhibition of TRPV1-mediated functional responses and abolished channel activation. Blocking the SR release (with ryanodine or dantrolene) led to a reduced capsaicin-induced Ca(2+) elevation suggesting that TRPV1 may participate to a secondary SR Ca(2+) liberation of greater amplitude. In conclusion, our experiments point out that TRPV1 is a functional SR Ca(2+) leak channel and may crosstalk with RyR1 in adult mouse muscle fibers.
authors.affiliation: Université Lyon 1, Centre National de la Recherche Scientifique UMR 5534, Centre de Génétique et de Physiologie Moléculaire et Cellulaire, Villeurbanne, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Lotteau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ducreux
authors.forename: Caroline
authors.initials: C
authors.lastname: Romestaing
authors.forename: Claude
authors.initials: C
authors.lastname: Legrand
authors.forename: Fabien
authors.initials: F
authors.lastname: Van Coppenolle
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium
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