NA-RECEPTOR CHANGES IN MUSCLE AT SITES DISTANT FROM BURNS DO NOT SIMULATE DENERVATION( CHANNEL AND ACETYLCHOLINE)

Muscle weakness and aberrant responses to neuromuscular relaxants afte r burn injury are associated with upregulation of acetylcholine recept ors (AChRs). Typically, these functional, pharmacological, and biochem ical changes occur after denervation, in which transcriptionally media ted qualitative changes in AChRs and Na+ channels and of myogenic regu latory proteins MyoD and myogenin also occur. This study in rats, by a n examination of changes in the above-enumerated proteins or their tra nscripts in the gastrocnemius muscle distant from the burn, verifies w hether a denervation-like state exists after burns. Scatchard analysis of [H-3]saxitoxin binding revealed no changes in the affinity (K-d) a nd total number (B-max) of Na+ channels between control and burn-injur ed animals at both 7 and 14 days after injury. The mRNA levels of the immature proteins, SkM2 of the Na+ channels and the gamma-subunits of AChRs, the increase of which is pathognomic of denervation, were asses sed by Northern analysis and were unchanged. The transcripts of mature Na+ channels, SkM1, were significantly increased at day 14 after the burn (1.24 +/- 0.10 in burn-injured vs. 1.06 +/- 0.12 in sham animals, arbitrary units, P = 0.006). Although MyoD levels were increased in b urn-injured animals at 14 days (0.21 +/- 0.02 vs. 0.15 +/- 0.07 arbitr ary units, P = 0.05), myogenin levels were unaltered. The absence of c hanges in AChR transcripts, including alpha-, delta-, and gamma-subuni ts, indicates that the upregulation of AChR in burns is not transcript ionally mediated. The unaltered levels of transcripts of myogenin, SkM 2 of Na+ channels and gamma-subunit of AChR, confirm that there is no denervation-like prejunctional (nerve-related) component to explain th e muscle weakness or the upregulation of AChRs at sites distant from b urns.