Sodium channel and acetylcholine receptor changes in muscle at
sites distant from burn do not simulate denervation.
Nosek, M. T., and J. A. J. Martyn.
Department of Anaesthesiology and Critical Care, Harvard Medical
School; Anesthesia Services, Massachusetts General Hospital and
Shriners Burns Institute, Boston, MA 02114
APStracts 3:0565A, 1996.
Muscle weakness and aberrant responses to neuromuscular relaxants
following burn injury are associated with upregulation of
acetylcholine receptors (AChRs). Typically, these functional,
pharmacological and biochemical changes occur following denervation
where transcriptionally-mediated qualitative changes in AChRs, sodium
channels (NaChs) and of myogenic regulatory proteins, MyoD and
myogenin also occur. This study in rats, by examining changes in the
above enumerated proteins or their transcripts in the gastrocnemius
muscle distant from the burn, verifies if a denervation-like state
exists following burns. Scatchard analysis of 3H-saxitoxin (STX)
binding revealed no changes in the affinity (Kd) and total number
(Bmax) of NaChs between controls and burns at both 7 and 14 days
after injury. The mRNA levels of the immature proteins, SkM2 of NaCh,
and of the [delta]-subunits of AChR, whose increase is pathognomic of
denervation, were assessed by Northern analysis and were unchanged.
The transcripts of mature NaCh, SkM1, were significantly increased at
day 14 after the burn (1.24+/-0.10 in burns vs. 1.06+/-0.12 in shams,
arbitrary units, p=0.006). Although MyoD levels were increased in
burns at 14 days (0.21+/-0.02 vs. 0.15+/-0.07, arbitrary units,
p=0.05), myogenin levels were unaltered. The absence of changes in
AChR transcripts, including [alpha], [delta] and [delta]-subunits
indicate that the upregulation of AChR in burns is not
transcriptionally mediated. The unaltered levels of transcripts of
myogenin, SkM2 of NaCh and [delta]-subunit of AChR confirm that there
is no denervation-like prejunctional (nerve-related) component to
explain the muscle weakness or the upregulation of AChRs at sites
distant from burns.
Received 19 March 1996; accepted in final form 26 November 1996.
APS Manuscript Number A276-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996