Hong Wang1, Bin Yang, Yong-fu Xu, Tao Yan, Shi-tong Li. 1. Department of Anesthesiology, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China.
Abstract
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 epsilon-AChR and gamma-AChR. METHODS: Both innervated and denervated mouse muscle cells, and human embryonic kidney 293 (HEK293) cells expressing epsilon-AChR or gamma-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 micromol/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, 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 gamma-AChR than epsilon-AChR (IC(50) values: 35.9 vs 22.3 nmol/L, P<0.01), VEC was equipotent at both receptor subtypes (IC(50) values: 9.9 vs 10.2 nmol/L, P>0.05), while ROC was more potent at gamma-AChR than epsilon-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.
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 epsilon-AChR and gamma-AChR. METHODS: Both innervated and denervated mouse muscle cells, and humanembryonic kidney 293 (HEK293) cells expressing epsilon-AChR or gamma-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 micromol/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, 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 gamma-AChR than epsilon-AChR (IC(50) values: 35.9 vs 22.3 nmol/L, P<0.01), VEC was equipotent at both receptor subtypes (IC(50) values: 9.9 vs 10.2 nmol/L, P>0.05), while ROC was more potent at gamma-AChR than epsilon-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.