Inactivity-induced remodeling of neuromuscular junctions in rat diaphragmatic muscle

We hypothesized that inactivity-induced remodeling of neuromuscular junctio ns (NMJs) depends on fiber type and the match between muscle fiber and moto neuron (MN) activities. Two inactivity models were studied in rat diaphragm atic muscle: spinal hemisection at C2 (SH), where both diaphragmatic muscle fibers and phrenic MNs were inactive, and tetrodotoxin (TTX) nerve blockad e, where only muscle fibers were inactive. After 2 weeks of inactivity, the re was increased number of pre- and postsynaptic branches (fragmentation) o f NMJs at type IIx/b fibers in both models. In addition, planar NMJ areas a t type IIx/b fibers in the SH model were enlarged. In contrast, NMJs at typ e I and IIa fibers were unaffected in both SH and TTX models. Functionally, neuromuscular transmission in diaphragmatic muscle fibers improved in the SH model, but worsened in the TTX model, compared to controls, These result s suggest that NMJ remodeling depends on the level of MN activity. The rela tive preservation of NMJs at type I and IIa fibers suggests a potential for recovery from diaphragmatic paralysis in the clinical setting, at least fo r respiratory behaviors. (C) 1999 John Wiley & Sons, Inc.