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J Appl Physiol 105: 527-537, 2008. First published May 29, 2008; doi:10.1152/japplphysiol.01145.2007
8750-7587/08 $8.00
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FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury

Benjamin T. Corona,1 Clement Rouviere,1 Susan L. Hamilton,2 and Christopher P. Ingalls1

1Muscle Biology Laboratory, Department of Kinesiology and Health, Georgia State University, Atlanta, Georgia; and 2Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas

Submitted 25 October 2007 ; accepted in final form 23 May 2008

Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction uncoupling. FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [ryanodine receptor (RyR1)] and plays an important role in excitation-contraction coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (tibialis anterior and extensor digitorum longus muscles) strength in skeletal muscle-specific FKBP12-deficient and wild-type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts. Histological damage of the tibialis anterior muscle was assessed after injury. Body weight and peak isometric and eccentric torques were lower in FKBP12-deficient mice compared with WT mice. There were no differences between FKBP12-deficient and WT mice in preinjury peak isometric and eccentric torques when normalized to body weight, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12-deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice, despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12-deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice.

mouse; skeletal muscle; damage; force; recovery



Address for reprint requests and other correspondence: C. P. Ingalls, Georgia State Univ., Dept. of Kinesiology and Health, P. O. Box 3975, Atlanta, GA 30302-3975 (e-mail: cingalls{at}gsu.edu)







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