Receptor analysis of differential sensitivity change to succinylcholine induced by nerve injury in rat gastrocnemius

BackgroundUrgent tracheal intubation is common in intensive care units and the emergency room, and succinylcholine is a first-line neuromuscular blocker used in these situations. Paraplegic or critically ill patients may be at a high risk of receiving succinylcholine because the denervation stage changes nicotinic receptors, which affect the efficacy and safety of succinylcholine. The objective of this study was to determine the receptor subtypes associated with changes in the pharmacodynamics of succinylcholine and its time-line trend.MethodsDenervated gastrocnemius was collected from tibial nerve transected rats. To determine the 50% effective dose of succinylcholine and rocuronium at 0 (control), 1, 3, 7, 14, and 28 d after denervation, action potential amplitude was monitored by an intracellular recording method. Subunits α1, α7, ε, and γ of the acetylcholine receptor (AChR) were quantified by real-time polymerase chain reaction. Receptor amount and pharmacodynamic changes were analyzed by correlation and regression analysis.ResultsThe pharmacodynamic change in succinylcholine was a dynamic process, and at the same time α7, ε, and γ-nicotinic AChR genes in denervated muscle were significantly changed but only α7 was closely correlated with the action of succinylcholine. Subunit γ and α7 were related to pharmacodynamic change in the nondepolarizing neuromuscular agent, rocuronium.ConclusionsNerve injury may alter nicotinic AChR subtypes in skeletal muscle at different stages, which probably affected the pharmacodynamics of neuromuscular blockers in different ways. Denervation time and stage and the type of neuromuscular blocker and dosage should be taken into consideration when using these drugs in patients with nerve injury.