From the discovery that the fast and slow physiological properties of muscles were a reflection of their content of a variety of biochemically distinct ‘fast’ and ‘slow’ muscle fibres, there sprang a lively debate as to the basis of this specialization by the individual fibres (reviewed in Kelly & Rubinstein, 1994). A paper published in this issue of The Journal of Physiology (Kalhovde et al. 2005) marks a major move in this debate from the developmental to the postnatal arena. This is a particular form of the question as to how neighbouring cells of similar developmental origin can diversify to express distinct suites of genes in a coordinated manner. In the case of skeletal muscle, there is the complication that each cell is a large syncytium in which numerous nuclei must be coordinated to the common pattern of gene expression required to achieve this effect. It is made more intriguing by the fact that the behaviour of each syncytium can be modified by the pattern of activity imposed upon it by its motor innervation. Subsequent research has revealed some complexity in the detail but a general picture has emerged that invokes the dual influences of innate programmed predilections of the muscle fibre interacting with the partly or wholly over-riding influence of the motor nerve. The neural influence has been much the easier to establish. It was achieved in a landmark paper (Buller et al. 1960) showing that experimentally cross-innervated ‘fast’ and ‘slow’ muscles acquired the physiological type that corresponded to the innervating motor nerve. Most of the evidence for an autonomous predisposition of muscle cells has come from developmental studies, perhaps most clearly from grafts made between the chick and the quail of the somites that give rise to breast muscles with the outcome that distinctive patterns of fast and slow fibres in these muscles were characteristic of the species of origin of the graft (Nikovits et al. 2001). Developmental studies in rodents have related the primary and secondary cohorts of muscle fibres in developing limb muscles to the eventual type of the fibre in the adult, primary fibres tending to become the ‘slow’ fibres of the adult with the secondary fibres showing a bias towards the fast phenotypes. Clearly, this equivalence is not complete, for some muscles become almost entirely slow in the adult while, in mice, most muscles become completely ‘fast’, and there must therefore be conversion from the developmental pattern to achieve this. It is yet to be fully established whether the predilections of developmental muscle precursor cells are passed on to the satellite cells that maintain growth and regeneration of muscle in postnatal life, for there is increasing evidence that satellite cells differ fundamentally from the prenatal muscle precursors. Postnatal investigations are complicated by the matter of disentangling the neural influence from any innate bias in the satellite cells. Tissue culture has shown that fibres formed by fusion of satellite cells in culture tend to express the same myosin isoforms as their parent fibre (Rosenblatt et al. 1996); but tissue culture introduces its own artefacts, not least the failure to reproduce normal patterns of muscle gene expression. In the study by Kalhovde et al. (2005) the effects of innervation in vivo have been cleverly nullified by denervating the muscle prior to killing it with bupivacaine, a muscle fibre-specific toxin, and maintaining muscle activity with an artificial ‘slow’ pattern of electrical stimulation. Comparison of the regenerated muscle in the slow soleus and fast extensor digitorum longus muscles subjected to bouts of stimulation at 20 Hz revealed that each muscle tended to regenerate the range of fibre types that characterize the pre-injury muscle. This shows convincingly that some memory of the previous profile of fibre types resides in the muscle and survives a cycle of degeneration and regeneration. The authors' favoured candidate for this repository of memory is the satellite cell, and this certainly fits with the tissue culture studies. Nonetheless, the case is not quite watertight; the basement membrane that surrounds each muscle fibre is known to contain informative structures and, since it persists through a bout of degeneration and regeneration, is a plausible alternative. Bearing in mind the increasing evidence of intercommunication between stem cells and their matrix, this dichotomy may be spurious, the persistence of fibre type proclivity lying perhaps in this cell–matrix partnership rather than in either specific site.
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Feb 14, 2024
Le Xiao + 12
Open Access