Activated calcineurin ameliorates contraction-induced injury to skeletal muscles of mdx dystrophic mice

Stupka, Nicole, Plant, David R., Schertzer, Jonathon D., Emerson, Tennent, Bassel-Duby, Rhonda, Olson, Eric N. and Lynch, Gordon S. 2006, Activated calcineurin ameliorates contraction-induced injury to skeletal muscles of mdx dystrophic mice, Journal of physiology, vol. 575, no. 2, pp. 645-656.


Title Activated calcineurin ameliorates contraction-induced injury to skeletal muscles of mdx dystrophic mice
Author(s) Stupka, Nicole
Plant, David R.
Schertzer, Jonathon D.
Emerson, Tennent
Bassel-Duby, Rhonda
Olson, Eric N.
Lynch, Gordon S.
Journal name Journal of physiology
Volume number 575
Issue number 2
Start page 645
End page 656
Publisher Wiley-Blackwell
Place of publication London, England
Publication date 2006-06-22
ISSN 0022-3751
1469-7793
Summary Utrophin expression is regulated by calcineurin and up-regulating utrophin can decrease the susceptibility of dystrophic skeletal muscle to contraction-induced injury. We overexpressed the constitutively active calcineurin-A α in skeletal muscle of mdx dystrophic mice (mdx CnA*) and examined the tibialis anterior muscle to determine whether the presence of activated calcineurin promotes resistance to muscle damage after lengthening contractions. Two stretches (10 s apart) of 40% strain relative to muscle fibre length were initiated from the plateau of a maximal isometric tetanic contraction. Muscle damage was assessed 1, 5 and 15 min later by the deficit in maximum isometric force and by quantifying the proportion of muscle fibres staining positive for intracytoplasmic albumin. The force deficit at all time points after the lengthening contractions was approximately 80% in mdx muscles and 30% in mdxCnA* muscles. The proportion of albumin-positive fibres was significantly less in control and injured muscles from mdxCnA* mice than from mdx mice. Compared with mdx mice, mean fibre cross-sectional area was 50% less in muscles from mdxCnA* mice. Furthermore, muscles frommdxCnA* mice exhibited a higher proportion of fibres expressing the slow(er) myosin heavy chain (MyHC) I and IIa isoforms, prolonged contraction and relaxation times, lower absolute and normalized maximum forces, and a clear leftward shift of the frequency–force relationship with greater force production at lower stimulation frequencies. These are structural and functional markers of a slower muscle phenotype. Taken together, our findings show that muscles from mdxCnA* mice have a smaller mean fibre cross-sectional area, a greater sarcolemmal to cytoplasmic volume ratio, and an increase in utrophin expression, promoting an attenuated susceptibility to contraction-induced injury. We conclude that increased calcineurin activity may confer functional benefits to dystrophic skeletal muscles.
Language eng
Field of Research 060110 Receptors and Membrane Biology
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, The Authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30019976

Document type: Journal Article
Collection: Institute for Technology Research and Innovation
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 33 times in TR Web of Science
Scopus Citation Count Cited 34 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 357 Abstract Views  -  Detailed Statistics
Created: Mon, 28 Sep 2009, 17:23:18 EST by Nicole Stupka

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.