Acetylcholine receptor subunit mRNA changes in burns are different from those seen after denervation: the 1993 Lindberg Award.
Neuromuscular dysfunction of burn trauma is evidenced as muscle weakness and altered sensitivity to neuromuscular relaxants. A biochemical characteristic of the neuromuscular dysfunction is the proliferation and spread of acetylcholine receptors (AChR) throughout the skeletal muscle membrane. Depending on whether the neuromuscular dysfunction is presynaptic, synaptic, or postsynaptic in origin, the transcripts that induce the proliferation of AChR differ. This study, by quantitation of mRNA transcripts of AChR in muscle, attempts to characterize the cause of the neuromuscular dysfunction of burn trauma. Examination of the levels of mRNA encoding alpha, beta, epsilon, gamma, and delta subunits of AChR with northern blot analysis indicate significant (p < 0.03) elevations of beta-subunit mRNA with a trend for increased levels of alpha and delta transcripts. An increase of gamma-subunit mRNA, typical of presynaptic or nerve-mediated neuromuscular dysfunction, was not observed after burns. That neuronal (presynaptic) factors do not cause the neuromuscular dysfunction was confirmed by the lack of elevation of transcripts of myoD and myogenin, which also increase in "denervation states." These findings indicate that the neuromuscular dysfunction of burn trauma is most likely related to synaptic or postsynaptic factors. Further characterization of the cause of the synaptic and postsynaptic neuromuscular changes in burns will have implications for the choice of therapeutic agents to rectify the neuromuscular dysfunction.
Ward
J M
JM
Department of Anesthesiology, Harvard Medical School, Boston, MA.
Rosen
K M
KM
Martyn
J A
JA
D000818:Animals; D001363:Awards and Prizes; D015152:Blotting, Northern; D002056:Burns / Q000503:physiopathology*; D015870:Gene Expression / Q000502:physiology; D008297:Male; D009132:Muscles / Q000294:innervation*; D017570:MyoD Protein / Q000235:genetics; D018008:Myogenin / Q000235:genetics; D009469:Neuromuscular Junction / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D012955:Societies, Medical; D014481:United States
D017570:MyoD Protein; C503803:Myog protein, rat; D018008:Myogenin; D012333:RNA, Messenger; D011950:Receptors, Cholinergic