Role of TRPC1 channel in skeletal muscle function.
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 Ca(2+) 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 Ca(2+) during repeated contractions and help muscles to maintain their force during sustained repeated contractions.
Laboratory of Cell Physiology, Inst. of Neuroscience, Université Catholique de Louvain, 55/40 av. Hippocrate, 1200 Brussels, Belgium. philippe.gailly@uclouvain.be
Nadège
N
Zanou
Georges
G
Shapovalov
Magali
M
Louis
Nicolas
N
Tajeddine
Chiara
C
Gallo
Monique
M
Van Schoor
Isabelle
I
Anguish
My Linh
ML
Cao
Olivier
O
Schakman
Alexander
A
Dietrich
Jean
J
Lebacq
Urs
U
Ruegg
Emmanuelle
E
Roulet
Lutz
L
Birnbaumer
Philippe
P
Gailly
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005784:Gene Amplification; D006579:Heterozygote; D007537:Isometric Contraction; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D018763:Muscle Fatigue / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000081406:Peptidyl-Prolyl Isomerase F; D017931:DNA Primers; C000631446:PPIF protein, mouse; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D004247:DNA; D021983:Cyclophilins; D002118:Calcium