Role of TRPC1 channel in skeletal muscle function
Journal article

Role of TRPC1 channel in skeletal muscle function

  • Zanou, Nadège Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
  • Shapovalov, Georges Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland;
  • Louis, Magali Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
  • Tajeddine, Nicolas Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
  • Gallo, Chiara Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland;
  • Van Schoor, Monique Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
  • Anguish, Isabelle Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland;
  • Cao, My Linh Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
  • Schakman, Olivier Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
  • Dietrich, Alexander Institute for Pharmacology and Toxicology, School of Medicine, University of Marburg, Marburg, Germany; and
  • Lebacq, Jean Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
  • Ruegg, Urs Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland;
  • Roulet, Emmanuelle Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland;
  • Birnbaumer, Lutz Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
  • Gailly, Philippe Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;
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Published in:
  • American Journal of Physiology-Cell Physiology. - American Physiological Society. - 2010, vol. 298, no. 1, p. C149-C162
English 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+]itransients 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.
Language
  • English
Open access status
green
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https://sonar.ch/global/documents/42809
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