The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading‐induced atrophy

Abstract

Key pointsr 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.r 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.r 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.Abstract 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.

Delay in weight bearing in surgically treated tibial shaft fractures is associated with impaired healing: a cohort analysis of 166 tibial fractures

“…Weight bearing after a fracture is important, as it helps to maintain bone and muscle mass and helps to return to daily life participation [ 13 , 14 ]. Moreover, through a process referred to as mechanotransduction weight bearing supports bone healing.…”

“…Not loading the bone for 8 weeks after a fracture reduces bone density up to 1 year after the fracture [ 12 ]. Additionally, prolonged inactivity quickly affects skeletal muscle tissue [ 13 ], leading to decreased mechanosensory function, atrophy and even increased energy expenditure on ambulation [ 14 ]. The aim of this study was to explore the relation between timing of weight bearing and fracture healing after tibial shaft fracture surgery.…”

Ambient and supplemental magnetic fields promote myogenesis via a TRPC1‐mitochondrial axis: evidence of a magnetic mitohormetic mechanism

“…We chose the aminoglycoside antibiotics to pharmacologically emulate the effects of magnetic shielding principally for their high reversibility, simple mechanism of blockage, and relatively low cytotoxicity, which eased interpretation of the results. The aminoglycoside antibiotics have been shown to sterically impede calcium permeation (open channel block) through small-conductance mechanically gated cation channels in skeletal muscle (71) as well as antagonize TRPC1 in muscle (17,59) where they are thought to represent the same or related entities (5)(6)(7)(8)(9). Despite the inference that the detected "stretch-activated" and TRP channels in skeletal muscle are synonymous, the capacity of the aminoglycoside antibiotics to block magnetic responses is supported by our results and is of high biological relevance.…”

“…Diverse transient receptor potential (TRP) channel family members have been implicated in numerous forms of cellular mechanosensation (4), and evidence exists that the mechanosensitive currents detected in muscle (5) correspond to a signaling complex containing TRPC1 (6). Accordingly, TRPC1 has been implicated in load‐dependent oxidative muscle development (7, 8). Exercise promotes oxidative muscle development, whereas inactivity results in the atrophy of oxidative muscle.…”

TRPCs: Influential Mediators in Skeletal Muscle

“…TRPC1 also participates in an adaptive response of skeletal muscle (i.e., muscle regeneration). Down-regulation of TRPC1 expression is required for the regrowth of the mouse soleus muscle after muscle atrophy and the inhibition of calcineurin (CaN) signaling is involved in the down-regulation of TRPC1 expression [122,123]. Additionally, the PI 3 K/Akt/p70S6K pathway plays an important role in muscle regeneration and development and Ca 2+ entry through TRPC1 has been shown to play a role in the activation of the PI 3 K/Akt/p70S6K pathway during the regenerating of TA and EDL muscles [124].…”