Reinnervated muscle fiber type-grouping-inevitable?

Muscle fiber-type grouping (‘clumping’) in cross-sections of patient muscle biopsies and the electrophysiological recordings of enlarged motor unit action potentials (MUAPs) are almost universally interpreted as peripheral nerve damage with subsequent reinnervation of denervated muscle fibers [1, 2]. Other electromyographic potentials, including nascent potentials, are indicators of early muscle reinnervation. Yet, after experimental reinnervation of large hindlimb cat muscles, muscle fiber-types and the muscle fibers innervated by a single motor nerve fiber, the muscle unit (MU) fibers, exhibit the mosaic distribution that is typical of all normally innervated muscles. Muscle fiber-type and MU fiber clumping become evident in large muscles only when few motor nerve fibers (20% or less) reinnervate these muscles after nerve transection and surgical repair [6]. These experimental findings in large hindlimb muscles may anticipate that muscle fiber-type and MU sprouting are not predictors of nerve damage and muscle reinnervation, as has been assumed. We addressed this possibility by examining the distributions of fiber-types and MU fibers in small muscles of the rat hindlimb for comparison with those in large muscles. Six months after nerve transection and repair, all the nerve fibers reinnervated the denervated rat muscle but, in contrast to the restored mosaic distribution of reinnervated MU fibers and fiber-types in well reinnervated large cat muscles, the reinnervated rat MU muscle fibers were mostly confined within 1-3 muscle fiber clumps; the MU fibers were clumped in parallel with a corresponding fiber-type grouping in the muscle crosssections [4]. Each MU muscle fiber is normally surrounded by an average of 6 non-MU muscle fibers and all the MU muscle fibers are confined to a ‘muscle territory’ that is bounded by the outermost MU fibers (Figure 1A, 1C). The territories occupy ~13% of the total muscle cross-sectional area in both small and large muscles [4]. The size of the MU territories decreases significantly after reinnervation of small but not the large muscles, the latter having many more muscle fibers. Normally, each motor nerve branches within intramuscular nerve sheathes to distribute the MU muscle fibers amongst non-MU fibers in a mosaic pattern (Figure 1A, 1C). The distal branching is more extensive in the large than the small muscles and the MU fibers are distributed in more muscle fascicles in the large as compared to the small muscles. Our interpretation is that regenerating nerves ‘miss’ some of the most proximal branch points in the intramuscular sheathes (Figure 1B, 1D) with the result that, in the small muscles, the Editorial