Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake.

The induction of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a key regulator of mitochondriogenesis, is well-established under multiple physical exercise regimens, including, endurance, resistance, and sprint training. We wanted to determine if increased expression of PGC-1alpha in muscle is sufficient to improve performance during exercise in vivo. We demonstrate that muscle-specific expression of PGC-1alpha improves the performance during voluntary as well as forced exercise challenges.

A naturally occurring calcineurin variant inhibits FoxO activity and enhances skeletal muscle regeneration.

The calcium-activated phosphatase calcineurin (Cn) transduces physiological signals through intracellular pathways to influence the expression of specific genes. Here, we characterize a naturally occurring splicing variant of the CnAbeta catalytic subunit (CnAbeta1) in which the autoinhibitory domain that controls enzyme activation is replaced with a unique C-terminal region. The CnAbeta1 enzyme is constitutively active and dephosphorylates its NFAT target in a cyclosporine-resistant manner.

Loaded wheel running and muscle adaptation in the mouse.

Voluntary cage wheel exercise has been used extensively to determine the physiological adaptation of cardiac and skeletal muscle in mice. In this study, we tested the effect of different loading conditions on voluntary cage wheel performance and muscle adaptation. Male C57Bl/6 mice were exposed to a cage wheel with no-resistance (NR), low-resistance (LR), or high-resistance (HR) loads for 7 wk.

Development of a mammalian series-fibered muscle.

This study examines the processes by which multiply innervated, serially fibered mammalian muscles are constructed during development. We previously reported that primary myotubes of such a muscle, the guinea pig sternomastoid muscle, span from tendon to tendon and are innervated at each of the muscle's four innervation zones. Secondary myotubes form later, in association with each point of innervation (Duxson and Sheard, Dev.

Intramuscular force transmission.

The architectural form of skeletal muscle, the pattern of activity/usage between neighbouring fibres, and the pathways for lateral and lengthwise tension delivery are all of interest in understanding muscle function and dysfunction. We have attempted to contribute to understanding of intramuscular force transmission by investigating the functional relationships between coactive motor units, and by examining the detailed molecular and morphological features at sites of tension transfer. We found that tension delivery is modulated by interaction between active and inactive fibres, that many muscle fibre terminations feature structural coupling between fibres, and that sites of tension delivery feature a variety of proteins including acetylcholinesterase, NCAM, dystrophin and two splice variants of the alpha7 integrins.

Localization of alpha 7 integrins and dystrophin suggests potential for both lateral and longitudinal transmission of tension in large mammalian muscles.

Non-primate mammalian muscles with fascicles above 35 mm in length are composed predominantly of arrays of short, non-spanning muscle fibres, which terminate within the belly of the muscle fascicle at one or both ends. We have previously described the morphological form of various muscle-to-muscle and muscle-to-matrix junctions which are likely involved in tension transmission within one such muscle - the guinea pig sternomastoid muscle (Young et al. 2000).

Different modes of hypertrophy in skeletal muscle fibers.

Skeletal muscles display a remarkable diversity in their arrangement of fibers into fascicles and in their patterns of innervation, depending on functional requirements and species differences. Most human muscle fascicles, despite their great length, consist of fibers that extend continuously from one tendon to the other with a single nerve endplate band. Other mammalian muscles have multiple endplate bands and fibers that do not insert into both tendons but terminate intrafascicularly.