Burn injury—induced nicotinic acetylcholine receptor changes on muscle membrane

Abstract

Patients with thermal injury show pharmacological responses akin to those seen following denervation of motor nerve where there is an increase in the number of muscle-type acetylcholine receptors (AChR). This study in the rat, examined the effect of 20%, 30%, and 50% body surface area burn injury on gastrocnemius and diaphragm AChR number, quantitated by [125I]alpha-bungarotoxin (alpha-BGT). Pharmacodynamic responses to D-tubocurarine were evaluated in the gastrocnemius muscle. AChR from gastrocnemius muscle were significantly increased in all burn groups at 14 days after burn. After 28 days, the AChR had returned to control in the 20% and 30% burn groups, but persisted in the 50% burn group. AChR from diaphragm did not show significant changes between groups. Resistance to D-tubocurarine was not seen in burn groups compared with controls. Burn trauma causes increases of AChR at sites distant from the area of injury. Diaphragm muscle may be less sensitive than gastrocnemius to mediators which upregulate AChR.

Uncoupling of in vivo torque production from EMG in mouse muscles injured by eccentric contractions

“…The difference we observed between the two groups of control muscles is consistent with the within-laboratory variation reported in the literature for rat gastrocnemius muscle AChR concentration (i.e. 5·7 vs. 30 fmol mg¢ from Kim et al (1995) and Ward & Martyn (1993), respectively).…”

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

“…Immobilization, as a contributing correlate to ICUAW (214), either resulted in increased (214,461) or unaltered receptor expression (337) in the immobilized limb. Finally, the condition "critical illness" also produced differential outcomes: upregulated (362,758) or unaltered (455) AChRs in thermal injury animal models, as well as in sepsis animal studies, depending on whether a panperitonitis CLP model [concluded downregulation at the neuromuscular endplate region (508); no change in AChR (595)] or chronic intravenous E. coli infection model (no upregulation of AChRs, Ref. 213) was employed.…”

Increased quantal release of acetylcholine at the neuromuscular junction following scald injury in the rat

“…10,11,29,30 Although one study describes a correlation between dTC resistance and nAChR upregulation after thermal injury in the rat, 10 other investigations have failed to demonstrate such a relationship. 14,23,29 Consequently, the precise contribution of nAChR upregulation to NDNB resistance remains unclear.…”

“…Marathe et al 14 reported no detectable change in nAChR number in rat diaphragm following a 30% BSA scald at 40 days after injury, a time at which their rats had previously exhibited maximal resistance to NDNB. 23 In contrast, Ward and Martyn 29 found that despite a significant increase in nAChR levels in rat gastrocnemius following 30% and 50% BSA scald, the same muscles were not resistant to the effects of dTC in vivo and, in fact, tended to be more sensitive to dTC than were controls. Many other factors could play a role in NDNB resistance after burn, including altered pharmacokinetics and plasma protein binding of dTC, altered affinity of nAChR for dTC, 19 and a decrease in acetylcholinesterase activity.…”