Résumé :
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Sarcoplasmic reticulum (SR) is an important compartment of the skeletal muscle cells involved in calcium release and calcium re-uptake during fibers contraction and relaxation. SR calcium concentration is mainly due to a balance between calcium release through Ryanodine Receptor 1 (RyR1) and re-uptake via Sarco Endoplasmic Reticulum Calcium ATPase (SERCA). Nevertheless there is very limited data available regarding other SR calcium leak channels.TRPV1 channel (Transient Receptor Potential Vanilloid 1) is opened by pH (acidosis), capsaicin and high temperature (>42_C). It is well known that this channel is implied in nociception. Nevertheless, previous studies have shown that TRPV1 channel, a cation-selective channel, is also expressed in the SR of a cell line from mouse muscle. This suggests that TRPV1 could act as a SR calcium leak channel in skeletal muscle cells. So, the purpose of the present study is to identify the localization and the physical role of TRPV1 in adult fully differentiated muscle fibers.In this study, using co-immuno-colocalization and confocal microscopy, we have shown that TRPV1 is expressed in mouse skeletal fibers from the Flexor Digitorum Brevis muscle. TRPV1 is close to SERCA pumps and distinct from RyR1 channels. It means that TRPV1 is located on the longitudinal part of the SR. In addition, using confocal microscopy and fluo-4 loaded cells to measure intracellular calcium, we show that capsaicin enhances SR calcium release. This effect is reduced after a pre-treatment with capsazepin, an inhibitor of TRPV1. Results thus strongly suggest that TRPV1 channel is a functional SR calcium leak channel.As TRPV1 stands in the longitudinal part of the SR, its calcium release activity is probably buffered by SERCA pumps. We will now focus our study on the physiopathological role of TRPV1 in skeletal muscle fibers during acidosis and fatigue.
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