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

作　　者：Hong WANG Bin YANG Yong-fu XU Tao YAN Shi-tong LI 

机构地区：[1]Department of Anesthesiology, First People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China

出　　处：《Acta Pharmacologica Sinica》2010年第4期399-404,共6页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by National Natural Science Foundation of China （No 30571796）.

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 （IC50） values （VEC： from 11.2 to 39.2 nmol/L, P〈0.01; ATR： from 24.4 to 129.0 nmol/L, P〈0.01; ROC： from 37.9 to 101.4 nmol/L, P〈0.01）. In HEK293 cell expression system, ATR was less potent at γ-AChR than ε-AChR （IC50 values： 35.9 vs 22.3 nmol/L, P〈0.01）, VEC was equipotent at both receptor subtypes （IC50 values： 9.9 vs 10.2 nmol/L, P〉0.05）, while ROC was more potent at γ-AChR than ε-AChR （IC50 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.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 （IC50） values （VEC： from 11.2 to 39.2 nmol/L, P〈0.01; ATR： from 24.4 to 129.0 nmol/L, P〈0.01; ROC： from 37.9 to 101.4 nmol/L, P〈0.01）. In HEK293 cell expression system, ATR was less potent at γ-AChR than ε-AChR （IC50 values： 35.9 vs 22.3 nmol/L, P〈0.01）, VEC was equipotent at both receptor subtypes （IC50 values： 9.9 vs 10.2 nmol/L, P〉0.05）, while ROC was more potent at γ-AChR than ε-AChR （IC50 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.

关 键 词：ACETYLCHOLINE ATRACURIUM DENERVATION nicotinic acetylcholine receptor ROCURONIUM nondepolarizing muscle relaxants VECURONIUM 

分 类 号：Q782[生物学—分子生物学] TQ463.4[化学工程—制药化工]