Different magnitude of resistance to nondepolarizing muscle relaxants in the denervated mouse skeletal muscle

摘要

Aim:To test the hypothesis that different magnitude of resistance of denervated skeletal muscle to nondepolarizing muscle relaxants (NDMRs) is related to their varying potencies at ε-AChR and γ-AChR.Methods:Both innervated and denervated mouse muscle cells, and human embryonic kidney 293 (HEK293) cells expressing ε-AChR or γ-AChR were used. The effects of NDMRs on nAChR were explored using whole-cell patch clamp technique.Results:NDMRs vecuronium (VEC), atracurium (ATR) and rocuronium (ROC) produced reversible, dose-dependent inhibition on the currents induced by 30 μmol/L acetylcholine both in innervated and denervated skeletal muscle cells. Compared to those obtained in innervated skeletal muscle cells, denervation shifted the concentration-response curves rightward and significantly increased the 50% inhibitory concentration (IC_(50)) values (VEC:from 11.2 to 39.2 nmol/L, P0.05), while ROC was more potent at γ-AChR than ε-AChR (IC_(50) values:22.3 vs 33.5 nmol/L, P<0.05).Conclusion:Magnitude differences of resistance to different NDMRs caused by denervation are associated with distinct potencies of NDMRs at nAChR subtypes.