肟硫磷中毒肌无力大鼠骨骼肌烟碱样乙酰胆碱受体通道特性

Properties of nicotinic acetylcholine receptors on muscle fibers in phoxim-induced myasthenic rats

目的 探讨肟硫磷引起肌无力大鼠骨骼肌烟碱样乙酰胆碱受体 (nAChR)通道特性的改变 ,揭示其发生机制。方法 用ip 1 .1 5g·kg-1肟硫磷制作成年大鼠肌无力模型 ,同时ip 1 6mg·kg-1阿托品以对抗毒蕈碱样症状。染毒后 0 .5～ 2h,8只大鼠出现肌无力 ,7只大鼠肌力正常。将 3只肌无力大鼠于肌力恢复后 (染毒后 1 2～ 1 8h) ,其余大鼠于染毒2～ 3h后 ,断颈处死 ,取后肢趾短屈肌 ,酶解制备骨骼肌纤维 ,用膜片钳对肌纤维nAChR通道做单通道电流记录。结果 肌无力大鼠nAChR单通道开放频率、表观平均开放时间、平均开放时间和电导均显著低于对照组和肌力正常的染毒大鼠 ,且肌力恢复后 ,以上各参数均接近对照组。结论 肟硫磷中毒引起肌无力可能与肟硫磷导致或促进nAChR的脱敏 ,以及阻断nAChR通道的开放有关。

AIM To explore the changes of properties of nicotinic acetylcholine receptors(nAChR) on muscle fibers from phoxim induced myasthenic rats and its mechanism. METHODS Fifteen rats were intraperitoneally intoxicated by phoxim(1.15 g·kg -1 ) and dosed with atropine(16 mg·kg -1 ) as antagonist to muscarinic symptoms of poisoning rats. Among them, 8 developed myasthenia, and 7 non myasthenia within 2 h after exposure. Two to three hours after intoxication, the flexor digitorum brevis of hind foot was dissected, digested by collagenase typeⅠ(2 g·L -1 ), and dissociated into single muscle fibers, on which the nAChR single channel recording was performed at endplate with patch clamp in cell attached mode. RESULTS The nAChR channels of myasthenic rats decreased significantly in open frequency, apparent mean open time, mean open time, and conductance in comparison with those of control and non myasthenic rats, and became similar to those of control individuals after complete recovery from muscle weakness. CONCLUSION The results indicated that phoxim induced myasthenia by directly or indirectly desensitizing nAChR and blocking nAChR channels on muscle fibers.