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Updated: Jun 15, 2026

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
Published on: July 26, 2017
Regulation by scaffolding proteins of canonical transient receptor potential channels in striated muscle
J Sabourin1, C Cognard, Bruno Constantin
1Equipe Physiopathologie et Pharmacologie des Canaux Ioniques, Institut de Physiologie et Biologie Cellulaires, UMR Université de Poitiers/CNRS no. 6187, 86022 Poitiers Cedex, France.
Abstract:
Recent studies proposed a pivotal role of TRPC channels, in particular TRPC1, in the striated muscle tissue and in the development of calcium mishandling observed in dystrophin-deficient skeletal and cardiac muscle cells (Vandebrouck et al. in J Cell Biol 158:1089-1096, 2002; Williams and Allen in Am J Physiol Heart Circ Physiol 292:H846-H855, 2007; Stiber et al. in Mol Cell Biol 28:2637-2647, 2008). In skeletal muscle, TRPCs are proposed to function in a costameric macromolecular complex (Vandebrouck et al. in FASEB J 21:608-617, 2007; Gervasio et al. in J Cell Sci 121:2246-2255, 2008) in which scaffolding proteins and dystrophin are central components maintaining normal calcium entry (Stiber et al. in Mol Cell Biol 28:2637-2647, 2008; Sabourin et al. in J Biol Chem 284:36248-61, 2009). In this review, we shall summarize the roles played by scaffolding proteins in regulating the calcium entry through TRPC channels of skeletal muscle cells and the implications in muscle physiopathology. Interactions of TRPC1 with caveolin-3, Homer-1 and alpha-syntrophin will be addressed and these complexes will be compared with signalplex in other systems. The mechanosensitive function of scaffolding proteins will be discussed as well as interactions with TRPV2 channels regarding to calcium mishandling in Duchenne dystrophy.
Insights
Scaffolding proteins regulate calcium entry via TRPC channels in skeletal muscle, impacting muscle cell function. Dysfunctional calcium handling in Duchenne muscular dystrophy involves TRPC1 and TRPV2 interactions.
Area of Science:
- Muscle physiology and cell biology
- Ion channel function
- Molecular mechanisms of muscle disease
Background:
- Transient Receptor Potential Canonical (TRPC) channels, particularly TRPC1, are implicated in striated muscle.
- Calcium mishandling is a hallmark of dystrophin-deficient muscle cells.
- TRPCs function within costameric macromolecular complexes in skeletal muscle.
Purpose of the Study:
- To review the role of scaffolding proteins in regulating calcium entry through TRPC channels in skeletal muscle cells.
- To discuss the implications of these interactions in muscle physiopathology.
- To explore the role of TRPC1 and TRPV2 channels in calcium mishandling in Duchenne muscular dystrophy.
Main Methods:
- Literature review of studies on TRPC channels, scaffolding proteins, and muscle physiology.
- Analysis of molecular interactions within costameric complexes.
- Discussion of calcium dysregulation mechanisms in muscular dystrophy.
Main Results:
- Scaffolding proteins like caveolin-3, Homer-1, and alpha-syntrophin are central to normal calcium entry via TRPC1.
- These protein complexes form signalplexes that regulate ion channel activity.
- Mechanosensitive functions of scaffolding proteins and their interaction with TRPV2 channels are crucial in muscle pathology.
Conclusions:
- Scaffolding proteins play a critical role in modulating TRPC channel-mediated calcium entry in skeletal muscle.
- Dysregulation of these complexes contributes to calcium mishandling observed in muscular dystrophies.
- Understanding these interactions offers potential therapeutic targets for muscle diseases.
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