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J. Cell Biol.,
Volume 145, Number 3, May 3, 1999 633-642
* The Randall Institute, King's College London, London WC2B 5RL, United Kingdom; Physical training regulates muscle metabolic
and contractile properties by altering gene expression.
Electrical activity evoked in muscle fiber membrane
during physical activity is crucial for such regulation,
but the subsequent intracellular pathway is virtually unmapped. Here we investigate the ability of myogenin, a
muscle-specific transcription factor strongly regulated
by electrical activity, to alter muscle phenotype. Myogenin was overexpressed in transgenic mice using regulatory elements that confer strong expression confined to
differentiated post-mitotic fast muscle fibers. In fast
muscles from such mice, the activity levels of oxidative
mitochondrial enzymes were elevated two- to threefold, whereas levels of glycolytic enzymes were reduced
to levels 0.3-0.6 times those found in wild-type mice.
Histochemical analysis shows widespread increases in
mitochondrial components and glycogen accumulation.
The changes in enzyme content were accompanied by a
reduction in fiber size, such that many fibers acquired a
size typical of oxidative fibers. No change in fiber type-specific myosin heavy chain isoform expression was observed. Changes in metabolic properties without
changes in myosins are observed after moderate endurance training in mammals, including humans. Our data
suggest that myogenin regulated by electrical activity
may mediate effects of physical training on metabolic capacity in muscle.
Department of Pharmacology and
Molecular Biology, Washington University, St. Louis, Missouri 63110-1093; and § Department of Biology, University of Oslo,
Blindern N-0316, Oslo, Norway
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