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Research Article

Role of TRPC1 channel in skeletal muscle function

¹Catholic University of Louvain ²University of Geneva ³University of Marburg, Germany ⁴Division of Intramural Research

Submitted 3 June 2009 ; revised 6 October 2009 ; accepted in final form 19 October 2009

Skeletal muscle contraction is reputed not to depend on extracellular Ca²⁺. Indeed, stricto sensu, excitation-contraction coupling does not necessitate an entry of Ca²⁺. However, we previously observed that, during sustained activity (repeated contractions), an entry of Ca²⁺ is needed to maintain force production. In the present study, we evaluated the possible involvement of the TRPC1 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 fibres from TRPC1^-/- mice. The influx of Ca²⁺ through TRPC1 channels represents a minor part of the entry of Ca²⁺ into muscle fibres at rest and the activity of the channel is not store-dependent. The lack of TRPC1 does not affect [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^+/+ fibres and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1^-/- mice display a smaller fibre cross-sectional area, generate less force per cross section 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.

channel; calcium; TRPC1; muscle fatigue