Skeletal muscle is a heterogeneous, multinucleated, post-mitotic tissue that contains many functionally diverse fibre types that are capable of adjusting their phenotypic properties in response to altered contractile demands. This plasticity, or adaptability of skeletal muscle is largely dictated by variations in motoneuron firing patterns. For example, in response to increased tonic firing of slow motoneurons, which occurs during bouts of endurance training or chronic low-frequency stimulation (CLFS), skeletal muscle adapts by transforming from a faster to a slower phenotypic profile. CLFS is an animal model of endurance training that induces fast-to-slow fibre type transformations in the absence of fibre injury in the rat. The underlying signaling mechanisms regulating this fast-to-slow fibre type transformation, however, remain to be fully elucidated. It has been suggested that myogenic stem cells, termed satellite cells, may regulate and/or facilitate this transformational process. Therefore, the signaling mechanisms involved in CLFS-induced satellite cell activation as well as the role satellite cells may play in CLFS-induced skeletal muscle adaptation were investigated in rat. A pharmacological inhibitor of nitric oxide (NO) synthase, Nω-nitro-L-arginine methyl ester, was used to investigate CLFS-induced satellite cell activation in the absence of endogenous NO production. Results suggest that NO is required for early CLFS-induced satellite cell activation, but a yet-to-be defined pathway exists that is able to fully compensate in the absence of prolonged NO production. A novel method of satellite cell ablation (i.e. weekly focal γ-irradiation application) was used to investigate CLFS-induced skeletal muscle adaptation in the absence of a viable satellite cell population. Myosin heavy chain (MHC), an important structural and regulatory protein component of the contractile apparatus, was used as a cellular marker of the adaptive response to CLFS. Findings suggest that satellite cell activity may be required for early fast-to-slow MHC-based transformations to occur at the protein level without delay in the fast fibre population, and may also play an obligatory role in the final transformation from fast type IIA to slow type I fibres. Interestingly, additional results show that NO appears to be a key mediator of MHC isoform gene expression during CLFS-induced fast-to-slow fibre type transformations.

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