Alterations of diaphragm neuromuscular junctions with hypothyroidism

Hypothyroidism (HYPO) often manifests as neuromuscular symptoms; however, little is known about its effects an the neuromuscular junction (NMJ). The present study examined changes in NMJ morphology and neuromuscular transmission failure (NTF) in the rat diaphragm muscle (Di(mus)) after 3 wk of HYPO. Three-color fluorescence immunocytochemistry and confocal microscopy were used to simultaneously visualize nerve terminals and axons, motor end plates, and myosin heavy chain isoform expression in Di(mus) fibers. NTF was assessed in vitro by comparing muscle fatigue induced by nerve with that induced by direct muscle stimulation. Diameters of axons innervating type I fibers were 30% smaller in the HYPO Di(mus) than in control (CTL). Planar areas of nerve terminals and end plates on type I and IIa fibers were 15-35% smaller in HYPO than in CTL, The extent of overlap between nerve terminals and end plates of type I fibers Mras 10% less in HYPO. Susceptibility to NTF during repetitive nerve stimulation was 20% greater in the CTL Di(mus) than in HYPO; however, changes in NMJ morphology could not fully account for the effect of HYPO on NTF.