Effects of HI-6 on muscle acetylcholine receptor: analysis on minimal reaction model
Chen, H.C.; Bai, D.Y.; Jiang, Y.P.
Zhongguo Yao Li Xue Bao 17(5): 428-431
1996
ISSN/ISBN: 0253-9756 PMID: 9863166 Document Number: 456463
AIM: To study the action of 1-(2-hydroxyiminomethyl-1-pcyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane dichloride (HI-6) on skeletal muscle acetylcholine receptor (N-2-ChR). METHODS: N-2-ChR was expressed in Xenopus laevis oocyte after injection with mRNA extracted from denervated rat leg muscles. The inward membrane currents induced by various concentrations of carbamylcholine and effects of HI-6 or d-tubocurarine on the currents were measured with voltage clamp technique by fast cell flow of agents. The actions of HI-6 and d-tubocurarine on N-2-ChR were analyzed by using the minimal reaction model. RESULTS: K of 40-05, 156.00, and 334.67 mu-mol cntdot L-1 for HI-6, K of 0.02, 0.10, and 0.18 mu-mol cntdot L-1 for d-tubocurarine were obtained by using the competing for single acetylcholine (ACh)-binding site model, the competing for two ACh-binding sites model, and the noncompetitive inhibition model, respectively. CONCLUSION: HI-6 and d-tubocurarine competed for two ACh-binding sites of N-2-ChR with equal affinity to antagonize the effects of the agonist on N-2-ChR. The N-2-ChR inhibition by HI-6 is much weaker than that by d-tubocurarine.