You are not logged in.

Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor

Cannata, David. J, Finklestein, David. I, Gantois, Ilse, Teper, Yaroslav, Drago, John and West, Jan. M 2009, Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor, Journal of muscle research and cell motility, vol. 30, no. 1-2, pp. 73-83, doi: 10.1007/s10974-009-9177-x.

Attached Files
Name Description MIMEType Size Downloads

Title Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor
Author(s) Cannata, David. J
Finklestein, David. I
Gantois, Ilse
Teper, Yaroslav
Drago, John
West, Jan. M
Journal name Journal of muscle research and cell motility
Volume number 30
Issue number 1-2
Start page 73
End page 83
Total pages 11
Publisher Springer Netherlands
Place of publication Dordrecht, The Netherlands
Publication date 2009
ISSN 0142-4319
1573-2657
Keyword(s) Dystonia
Nicotinic acetylcholine receptor
S248F mutation
Skinned muscle fibre
Introduction
Summary

We generated a mouse line with a missense mutation (S248F) in the gene (CHRNA4) encoding the α4 subunit of neuronal nicotinic acetylcholine receptor (nAChR). Mutant mice demonstrate brief nicotine induced dystonia that resembles the clinical events seen in patients with the same mutation. Drug-induced dystonia is more pronounced in female mice, thus our aim was to determine if the S248F mutation changed the properties of fast- and slow-twitch muscle fibres from female mutant mice. Reverse transcriptase-PCR confirmed CHRNA4 gene expression in the brain but not skeletal muscles in normal and mutant mice. Ca2+ and Sr2+ force activation curves were obtained using skinned muscle fibres prepared from slow-twitch (soleus) and fast-twitch (EDL) muscles. Two significant results were found: (1) the (pCa50 - pSr50) value from EDL fibres was smaller in mutant mice than in wild type (1.01 vs. 1.30), (2) the percentage force produced at pSr 5.5 was larger in mutants than in wild type (5.76 vs. 0.24%). Both results indicate a shift to slow-twitch characteristics in the mutant. This conclusion is supported by the identification of the myosin heavy chain (MHC) isoforms. Mutant EDL fibres expressed MHC I (usually only found in slow-twitch fibres) as well as MHC IIa. Despite the lack of spontaneous dystonic events, our findings suggest that mutant mice may be having subclinical events or the mutation results in a chronic alteration to muscle neural input.

Language eng
DOI 10.1007/s10974-009-9177-x
Field of Research 111699 Medical Physiology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
HERDC collection year 2009
Copyright notice ©2009, Springer Science + Business Media B. V.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30032059

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 2 times in TR Web of Science
Scopus Citation Count Cited 2 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 528 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Wed, 22 Dec 2010, 11:00:13 EST by Teresa Treffry

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.