Heterogeneity in form and function of the rat extensor digitorum longus motor unit

The motor unit comprises a variable number of muscle fibres that connect through myelinated nerve fibres to a motoneuron (MN), the central drivers of activity. At the simplest level of organisation there exist phenotypically distinct MNs that activate corresponding muscle fibre types, but within an individual motor pool there typically exists a mixed population of fast and slow firing MNs, innervating groups of Type II and Type I fibres, respectively. Characterising the heterogeneity across multiple levels of motor unit organisation is critical to understanding changes that occur in response to physiological and pathological perturbations. Through a comprehensive assessment of muscle histology and ex vivo function, mathematical modelling and neuronal tracing, we demonstrate regional heterogeneities at the level of the MN, muscle fibre type composition and oxygen delivery kinetics of the rat extensor digitorum longus (EDL) muscle. Specifically, the EDL contains two phenotypically distinct regions: a relatively oxidative medial and a more glycolytic lateral compartment. Smaller muscle fibres in the medial compartment, in combination with a greater local capillary density, preserve tissue O(2) partial pressure (PO(2)) during modelled activity. Conversely, capillary supply to the lateral compartment is calculated to be insufficient to defend active muscle PO(2) but is likely optimised to facilitate metabolite removal. Simulation of in vivo muscle length change and phasic activation suggest that both compartments are able to generate similar net power. However, retrograde tracing demonstrates (counter to previous observations) that a negative relationship between soma size and C‐bouton density exists. Finally, we confirm a lack of specificity of SK3 expression to slow MNs. Together, these data provide a reference for heterogeneities across the rat EDL motor unit and re‐emphasise the importance of sampling technique.