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Title: The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading-induced atrophy
Authors: Xia, L
Cheung, KK 
Yeung, SS 
Yeung, EW 
Issue Date: 1-Jun-2016
Publisher: Wiley-Blackwell
Source: The journal of physiology, 1 June 2016, v. 594, no. 11, p. 3111-3126 How to cite?
Journal: The journal of physiology 
Abstract: Key points
- Decreased mechanical loading results in skeletal muscle atrophy. The transient receptor potential canonical type 1 (TRPC1) protein is implicated in this process. Investigation of the regulation of TRPC1 in vivo has rarely been reported. In the present study, we employ the mouse hindlimb unloading and reloading model to examine the involvement of TRPC1 in the regulation of muscle atrophy and regrowth, respectively.
- We establish the physiological relevance of the concept that manipulation of TRPC1 could interfere with muscle regrowth processes following an atrophy-inducing event. Specifically, we show that suppressing TRPC1 expression during reloading impairs the recovery of the muscle mass and slow myosin heavy chain profile. Calcineurin appears to be part of the signalling pathway involved in the regulation of TRPC1 expression during muscle regrowth.
- These results provide new insights concerning the function of TRPC1. Interventions targeting TRPC1 or its downstream or upstream pathways could be useful for promoting muscle regeneration.
Decreased mechanical loading, such as bed rest, results in skeletal muscle atrophy. The functional consequences of decreased mechanical loading include a loss of muscle mass and decreased muscle strength, particularly in anti-gravity muscles. The purpose of this investigation was to clarify the regulatory role of the transient receptor potential canonical type 1 (TRPC1) protein during muscle atrophy and regrowth. Mice were subjected to 14 days of hindlimb unloading followed by 3, 7, 14 and 28 days of reloading. Weight-bearing mice were used as controls. TRPC1 expression in the soleus muscle decreased significantly and persisted at 7 days of reloading. Small interfering RNA (siRNA)-mediated downregulation of TRPC1 in weight-bearing soleus muscles resulted in a reduced muscle mass and a reduced myofibre cross-sectional area (CSA). Microinjecting siRNA into soleus muscles in vivo after 7 days of reloading provided further evidence for the role of TRPC1 in regulating muscle regrowth. Myofibre CSA, as well as the percentage of slow myosin heavy chain-positive myofibres, was significantly lower in TRPC1-siRNA-expressing muscles than in control muscles after 14 days of reloading. Additionally, inhibition of calcineurin (CaN) activity downregulated TRPC1 expression in both weight-bearing and reloaded muscles, suggesting a possible association between CaN and TRPC1 during skeletal muscle regrowth.
ISSN: 0022-3751
EISSN: 1469-7793
DOI: 10.1113/JP271705
Rights: © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society
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