Am J Physiol Cell Physiol AJP: Cell Physiology
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Am J Physiol Cell Physiol 292: C440-C451, 2007. First published January 1, 2007; doi:10.1152/ajpcell.00085.2006
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year

Z. Ashley,1 H. Sutherland,1 H. Lanmüller,2 M. F. Russold,1 E. Unger,2 M. Bijak,2 W. Mayr,2 S. Boncompagni,3 F. Protasi,3 S. Salmons,1 and J. C. Jarvis1

1Muscle Research Group, Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool, United Kingdom; 2Centre for Biomedical Engineering and Physics, Medical University of Vienna, Allgemeines Krankenhaus, Vienna, Austria; and 3Interuniversity Institute of Myology, Centro Studi Industriali for Center, Research on Aging, Università degli Studi G. d'Annunzio, Chieti, Italy

Submitted 21 February 2006 ; accepted in final form 20 July 2006

Our understanding of the effects of long-term denervation on skeletal muscle is heavily influenced by an extensive literature based on the rat. We have studied physiological and morphological changes in an alternative model, the rabbit. In adult rabbits, tibialis anterior muscles were denervated unilaterally by selective section of motor branches of the common peroneal nerve and examined after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area by 50–60% and tetanic force by 75%, with no apparent reduction in specific force (force per cross-sectional area of muscle fibers). The loss of mass was associated with atrophy of fast fibers and an increase in fibrous and adipose connective tissue; the diameter of slow fibers was preserved. Within fibers, electron microscopy revealed signs of ultrastructural disorganization of sarcomeres and tubular systems. This, rather than the observed transformation of fiber type from IIx to IIa, was probably responsible for the slow contractile speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no significant differences. At no stage was there any evidence of necrosis or regeneration, and the total number of fibers remained constant. These changes are in marked contrast to the necrotic degeneration and progressive decline in mass and force that have previously been found in long-term denervated rat muscles. The rabbit may be a better choice for a model of the effects of denervation in humans, at least up to 1 yr after lesion.

force; shortening velocity; electron microscopy; histochemistry


Address for reprint requests and other correspondence: S. Salmons, Dept. of Human Anatomy and Cell Biology, School of Biomedical Sciences, Ashton St., Univ. of Liverpool, Liverpool L69 3GE, UK (e-mail: s.salmons{at}liverpool.ac.uk)






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