Background: Knowledge of the morphological and biochemical alterations occurring in skeletal muscles of obese animals is relatively limited, particularly with respect to non-limb muscles and relationship to fibre type. Objective: Sternomastoid (SM; fast-twitch), extensor digitorum longus (EDL; fast-twitch), and soleus (SOL; mixed) muscles of ob/ob mouse (18-22 weeks) were examined with respect to size (mass, muscle mass-to-body mass ratio, cross-sectional area (CSA)), fibre CSA, protein content, myosin heavy chain (MHC) content, MHC isoform (MHC i ) composition, MHC i -based fibre type composition, and lactate dehydrogenase isoenzyme (LDH iso ) composition. Results: Compared with (control) muscles from lean mice, all the three muscles from ob/ob mice were smaller in size (by 13-30%), with SM and EDL being the most affected. The CSA of IIB and IIB þ IID fibres (the predominant fibre types in SM and EDL muscles) was markedly smaller (by B30%) in ob/ob mice, consistent with differences in muscle size. Total protein content (normalised to muscle mass) was significantly lower in EDL (À9.7%) and SOL (À14.1%) muscles of ob/ob mice, but there were no differences between SM, EDL, and SOL muscles from the two animal groups with respect to MHC content (also normalised to muscle mass). Electrophoretic analyses of MHC i composition in whole muscle homogenates and single muscle fibres showed a shift towards slower MHC i content, slower MHC i containing fibres, and a greater proportion of hybrid fibres in all the three muscles of ob/ob mice, with a shift towards a more aerobic-oxidative phenotype also observed with respect to LDH iso composition. Conclusion: This study showed that SM, EDL, and SOL muscles of ob/ob mice display size reductions to an extent that seems to be largely related to fibre type composition, and a shift in fibre type composition that may result from a process of structural remodelling, as suggested by the increased proportion of hybrid fibres in muscles of ob/ob mice.

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In skeletal muscle, action potentials activate voltage sensors in the transverse tubular (T-) system, which open the Ca¥ release channels in the adjacent sarcoplasmic reticulum (SR), leading to a rise in cytoplasmic [Ca¥] and force development by the contractile apparatus (Melzer et al. 1995). Experiments with SR vesicles and single Ca¥ release channels indicate that channel activity is modulated by cytoplasmic Ca¥, Mg¥, ATP, pH and other factors (Meissner, 1984;Meissner et al. 1986Meissner et al. , 1997Laver et al. 1997). However, voltage sensor activation of the Ca¥ release channels is not always affected by cytoplasmic factors in the same way as is direct activation of isolated release channels. For example, depolarization-induced Ca¥ release in mechanically skinned fibres, which utilizes the normal voltage sensor control mechanism (Lamb & Stephenson, 1990), is largely unaffected by a reduction in cytoplasmic pH to •6•0 (Lamb et al. 1992;Lamb & Stephenson, 1994), whereas activation of Ca¥ release in SR vesicles by Ca¥ and ATP analogues is very strongly inhibited at such pH levels (Meissner, 1984). Here, we investigate whether depolarization-induced Ca¥ release in mammalian fibres is modulated by cytoplasmic [ATP] and whether this could contribute to the development of muscle fatigue. After prolonged stimulation of a muscle fibre, force production declines due both to effects on the contractile apparatus and to a reduction in Ca¥ release from the SR (Allen et al. 1995). The force response normally fully recovers within 30 min, except if the stimulation regime is extreme, when it can induce muscle fatigue lasting over many hours to days (often called 'low-frequency fatigue') possibly because of irreversible Ca¥-induced changes in protein interactions or triad structure (Lamb et al. 1995;Chin et al. 1997).