Impaired myofibrillar function in the soleus muscle of mice with collagen-induced arthritis

✍ Scribed by Takashi Yamada; Nicolas Place; Natalia Kosterina; Therese Östberg; Shi-Jin Zhang; Cecilia Grundtman; Helena Erlandsson-Harris; Ingrid E. Lundberg; Birgitta Glenmark; Joseph D. Bruton; Håkan Westerblad

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 236 KB
• Volume: 60
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.24907

✦ Synopsis

Abstract

Objective

Progressive muscle weakness is a common feature in patients with rheumatoid arthritis (RA). However, little is known about whether the intrinsic contractile properties of muscle fibers are affected in RA. This study was undertaken to investigate muscle contractility and the myoplasmic free Ca^2+^ concentration ([Ca^2+^]~i~) in the soleus, a major postural muscle, in mice with collagen‐induced arthritis (CIA).

Methods

Muscle contractility and [Ca^2+^]~i~ were assessed in whole muscle and intact single‐fiber preparations, respectively. The underlying mechanisms of contractile dysfunction were assessed by investigating redox modifications using Western blotting and antibodies against nitric oxide synthase (NOS), superoxide dismutase (SOD), 3‐nitrotyrosine (3‐NT), carbonyl, malondialdehyde (MDA), and S‐nitrosocysteine (SNO‐Cys).

Results

The tetanic force per cross‐sectional area was markedly decreased in the soleus muscle of mice with CIA, and the change was not due to a decrease in the amplitude of [Ca^2+^]~i~ transients. The reduction in force production was accompanied by slowing of the twitch contraction and relaxation and a decrease in the maximum shortening velocity. Immunoblot analyses showed a marked increase in neuronal NOS expression but not in inducible or endothelial NOS expression, which, together with the observed decrease in SOD2 expression, favors peroxynitrite formation. These changes were accompanied by increased 3‐NT, carbonyl, and MDA adducts content in myofibrillar proteins from the muscles of mice with CIA. Moreover, there was a significant increase in SNO‐Cys content in myosin heavy‐chain and troponin I myofibrillar proteins from the soleus muscle of mice with CIA.

Conclusion

These findings show impaired contractile function in the soleus muscle of mice with CIA and suggest that this abnormality is due to peroxynitrite‐induced modifications in myofibrillar proteins.