The myotubal origin of rat muscle fibres affects the extent of tenotomy-induced atrophy.

1. Immature muscle fibres (myotubes) can be divided into primary and secondary generations, which differ from each other in their time of formation, growth rates and myosin isoform expression. It is unclear whether the intrinsic differences between primary and secondary myotubes are totally extinguished once they mature and extrinsic factors, such as load, become important. 2. Four pregnant rats were injected with 5-bromo-2'-deoxyuridine (BrdU) on the 14th and 15th days of gestation. This selectively and permanently labels primary myotubes. Ten rats from four litters were killed when 8 months old, with three males (365-430 g) from a single litter being used for the quantitative study and the remainder being examined qualitatively. The extensor digitorum longus muscle (EDL) in each rat was tenotomized for 14 days. The sizes of fibres in the EDL were then correlated with their fibre type and whether they contained BrdU-labelled nuclei. 3. We reported that (i) II A and II B fibres derived from primary myotubes atrophied significantly less after tenotomy than II A and II B fibres derived from secondary myotubes and (ii) BrdU-labelled myonuclei were retained in the tenotomized muscle, even though tenotomy resulted in a substantial loss of myonuclei from the EDL. 4. We conclude that the origin of a fibre is a determinant of its response to the external forces which control its size, and hence force generation.