Role of TRPC1 channel in skeletal muscle function
(2010) American Journal of Physiology: Cell Physiology — Vol. 298, n° 1, p. C149-C162 (2010)
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- Zanou N, Shapovalov G, Louis M, Tajeddine N, Gallo C, Van Schoor M, Anguish I, Cao ML, Schakman O, Dietrich A, Lebacq J, Ruegg U, Roulet E, Birnbaumer L, Gailly P. Role of TRPC1 channel in skeletal muscle function. Am J Physiol Cell Physiol 298: C149-C162, 2010. First published October 21, 2009; doi:10.1152/ajpcell.00241.2009.-Skeletal muscle contraction is reputed not to depend on extracellular Ca2+. Indeed, stricto sensu, excitation-contraction coupling does not necessitate entry of Ca2+. However, we previously observed that, during sustained activity (repeated contractions), entry of Ca2+ is needed to maintain force production. In the present study, we evaluated the possible involvement of the canonical transient receptor potential (TRPC) 1 ion channel in this entry of Ca2+ and investigated its possible role in muscle function. Patch-clamp experiments reveal the presence of a small-conductance channel (13 pS) that is completely lost in adult fibers from TRPC1(-/-) mice. The influx of Ca2+ through TRPC1 channels represents a minor part of the entry of Ca2+ into muscle fibers at rest, and the activity of the channel is not store dependent. The lack of TRPC1 does not affect intracellular Ca2+ concentration ([Ca2+](i)) transients reached during a single isometric contraction. However, the involvement of TRPC1-related Ca2+ entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1(-/-) mice stimulated repeatedly progressively display lower [Ca2+](i) transients than those observed in TRPC1(-/-) fibers, and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1(-/-) mice display a smaller fiber cross-sectional area, generate less force per cross-sectional area, and contain less myofibrillar proteins than their controls. They do not present other signs of myopathy. In agreement with in vitro experiments, TRPC1(-/-) mice present an important decrease of endurance of physical activity. We conclude that TRPC1 ion channels modulate the entry of Ca2+ during repeated contractions and help muscles to maintain their force during sustained repeated contractions.
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Zanou, N., Shapovalov, G., Louis, M., Tajeddine, N., Gallo, C., Van Schoor, M., Anguish, I., Cao, M. L., Schakman, O., Dietrich, A., Lebacq, J., Ruegg, U., Roulet, E., Birnbaumer, L., & Gailly, P. (2010). Role of TRPC1 channel in skeletal muscle function. American Journal of Physiology: Cell Physiology, 298(1), C149-C162. https://doi.org/10.1152/ajpcell.00241.2009 (Original work published 2010)