APPS November 2002 Meeting Abstract 2401

Insulin-like growth factor-I (IGF-I) is a potent anabolic agent in skeletal muscle responsible for increasing rates of protein and nucleic acid synthesis, as well as inhibiting protein degradation. Recent evidence indicates that IGF-I has potential for ameliorating the muscle wasting and weakness associated with neuromuscular disorders, including the muscular dystrophies.¹ Little is known about the effects of IGF-I on contractile function at the cellular level. The purpose of this study was to determine whether the improvement in muscle function of IGF-I treated dystrophic mice was mediated by an alteration in contractile activation characteristics of single muscle fibres. We tested the null hypothesis that IGF-I treatment would not alter the contractile characteristics of single muscle fibres from dystrophic mdx or control mice. Following IGF-I administration (1 mg/kg s.c. via mini osmotic pump for 8 weeks), (C57BL/10; n = 8) and mdx (n = 8) mice were anaesthetised with sodium pentobarbitone (60-80 mg/kg) and the fast twitch extensor digitorum longus (EDL) muscles excised, and placed in a glycerol-based solution to permeate the muscle membranes. Dissected permeabilized fibre segments were activated in a series of Ca²⁺- and Sr²⁺-buffered solutions to determine the force-pCa (-pSr) relationship. There was no difference in fibre sensitivity to Ca²⁺ or Sr²⁺ nor was there any difference in force output per cross-sectional area between fibres from IGF-I treated and untreated control or mdx mice. We conclude that in isolated fibres from fast twitch muscles of control and mdx mice, IGF-I treatment does not affect Ca²⁺ sensitivity or intrinsic force producing capacity.