TRPC3 channels confer cellular memory of recent neuromuscular activity.
Skeletal muscle adapts to different patterns of motor nerve activity by alterations in gene expression that match specialized properties of contraction, metabolism, and muscle mass to changing work demands (muscle plasticity). Calcineurin, a calcium/calmodulin-dependent, serine-threonine protein phosphatase, has been shown to control programs of gene expression in skeletal muscles, as in other cell types, through the transcription factor nuclear factor of activated T cells (NFAT). This study provides evidence that the function of NFAT as a transcriptional activator is regulated by neuromuscular stimulation in muscles of intact animals and that calcium influx from the transient receptor potential (TRPC3) channel is an important determinant of NFAT activity. Expression of TRPC3 channels in skeletal myocytes is up-regulated by neuromuscular activity in a calcineurin-dependent manner. These data suggest a mechanism for cellular memory in skeletal muscles whereby repeated bouts of contractile activity drive progressively greater remodeling events.
Rosenberg
Paul
P
Department of Internal Medicin, Duke University Medical School, Durham, 27710, USA. rosen029@mc.duke.edu
Hawkins
April
A
Stiber
Jonathan
J
Shelton
John M
JM
Hutcheson
Kelley
K
Bassel-Duby
Rhonda
R
Shin
Dong Min
DM
Yan
Zhen
Z
Williams
R Sanders
RS
D000818:Animals; D019703:Calcineurin / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000302:isolation & purification / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology; D050778:NFATC Transcription Factors; D009469:Neuromuscular Junction / Q000502:physiology*; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050052:TRPC Cation Channels; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D007473:Ion Channels; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D014157:Transcription Factors; D019703:Calcineurin; D002118:Calcium