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TRPC3 channels confer cellular memory of recent neuromuscular activity
Paul Rosenberg *,
April Hawkins *,
Jonathan Stiber *,
John M. Shelton,
Kelley Hutcheson *,
Rhonda Bassel-Duby,
Dong Min Shin,
Zhen Yan *, and
R. Sanders Williams *,
*Departments of Internal Medicine and Pharmacology, Duke University Medical School, Durham, NC 27710; Department of Molecular Biology and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; and Department of Oral Biology, Yonsei University, Seoul 120-749, South Korea
Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA
Accepted for publication May 11, 2004.
Received for publication December 9, 2003.
Abstract:
Skeletal muscle adapts to different patterns of motor nerveactivity by alterations in gene expression that match specializedproperties of contraction, metabolism, and muscle mass to changingwork demands (muscle plasticity). Calcineurin, a calcium/calmodulin-dependent,serine–threonine protein phosphatase, has been shown tocontrol programs of gene expression in skeletal muscles, asin other cell types, through the transcription factor nuclearfactor of activated T cells (NFAT). This study provides evidencethat the function of NFAT as a transcriptional activator isregulated by neuromuscular stimulation in muscles of intactanimals and that calcium influx from the transient receptorpotential (TRPC3) channel is an important determinant of NFATactivity. Expression of TRPC3 channels in skeletal myocytesis up-regulated by neuromuscular activity in a calcineurin-dependentmanner. These data suggest a mechanism for cellular memory inskeletal muscles whereby repeated bouts of contractile activitydrive progressively greater remodeling events.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: NFAT, nuclear factor of activated T cells; RYR,ryanodine receptor; CPA, cyclopiazoic acid; EDL, extensor digitorumlongus.
To whom correspondence should be addressed at: Duke University Medical Center, Box 2927, Durham, NC 27710. E-mail: rosen029{at}mc.duke.edu.
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,
Kelley Hutcheson *,
Rhonda Bassel-Duby 
,
Zhen Yan *, and
R. Sanders Williams *, 
To whom correspondence should be addressed at: Duke University Medical Center, Box 2927, Durham, NC 27710. E-mail: 
