Neurological and Motor Disorders: TRPC in the Skeletal Muscle

Abstract

Transient receptor potential canonical (TRPC) channels belong to the large family of TRPs that are mostly nonselective cation channels with a great variety of gating mechanisms. TRPC are composed of seven members that can all be activated downstream of agonist-induced phospholipase C stimulation, but some members are also stretch-activated and/or are part of the store-operated Ca entry (SOCE) pathway. Skeletal muscles generate contraction via an explosive increase of cytosolic Ca concentration resulting almost exclusively from sarcoplasmic reticulum Ca channel opening. Even if neglected for a long time, it is now commonly accepted that Ca entry via SOCE and other routes is essential to sustain contractions of the skeletal muscle. In addition, Ca influx is required during muscle regeneration, and alteration of the influx is associated with myopathies. In this chapter, we review the implication of TRPC channels at different stages of muscle regeneration, in adult muscle fibers, and discuss their implication in myopathies.

TRPCs: Influential Mediators in Skeletal Muscle

“…Various TRP isoforms have been identified in mouse skeletal muscle. Regarding the case of the TRPC subfamily, TRPC1, TRPC3, TRPC4 and TRPC6 expression has mainly been found in skeletal muscle (TRPC2 is a pseudogene in humans) [38,53,61,74,[110][111][112]. There are controversies about the expression level of TRPC5 and TRPC7 in skeletal muscle.…”

“…STIM1L, a splice variant of STIM1 with additional residues in the cytosolic region, has been identified in skeletal muscle [42,43,52]. The silencing of STIM1L induces a significant delay in the activation of SOCE and the formation of small myotubes, and the effects of STIM1L overexpression are the opposite of those caused by STIM1L silencing [34,42,52,61]. Added to the positional advantage of STIMs and Orais at the triad junction (i.e., the preformation of puncta), it has been proposed that the formation of a permanent STIM1L-Orai1 complex also could be responsible for the faster activation of SOCE in skeletal muscle cells than in other types of cells [42].…”

The Complex Role of Store Operated Calcium Entry Pathways and Related Proteins in the Function of Cardiac, Skeletal and Vascular Smooth Muscle Cells

“…These clusters are responsible for the rapid (<1 s) activation of SOCE in skeletal muscle in comparison with other cells (Rosado et al, 2016 ). STIM1L is colocalized with Orai1 as well as others channels, such as TRPC1, TRPC3, TRPC4, and TRPC6 (Horinouchi et al, 2012 ; Antigny et al, 2017 ; Saüc and Frieden, 2017 ). STIM1L silencing evokes significant delay in SOCE activation and promotes the formation of small myotubes.…”

“…STIM1L silencing evokes significant delay in SOCE activation and promotes the formation of small myotubes. In contrast, STIM1L overexpression accelerates SOCE activation and triggers the formation of larger myotubes (Darbellay et al, 2011 ; Horinouchi et al, 2012 ; Antigny et al, 2017 ; Saüc and Frieden, 2017 ).…”

“…In skeletal muscle, several isoforms of the TRPC subfamily are expressed (Saüc and Frieden, 2017 ). In particular, TRPC1, TRPC3, TRPC4, and TRPC6 have been consistently found in cultured myoblasts or in adult muscles (Gailly, 2012 ; Antigny et al, 2013 ).…”