The effects of muscle relaxants on adult-type and fetal-type nictinic acetylcholine receptors

利用非洲爪哇卵母细胞表达系统比较了激动剂和竞争性拮抗剂对牛肌肉成年型(结合型)和胎儿型(节外型)烟碱型乙酰胆碱受体(NAChR)的影响。成人型nAChR对乙酰胆碱(ACh)和琥珀酸胆碱(Sch)的Km值与胎儿型无显著差异。成人型nAChR在ACh或SCH为300um时，电流衰减的时间常数比胎儿型快，电流可用单指数函数近似(p&lt；0.05)。在1 mm处，SCH对开放的离子通道有很强的阻断作用。在双脉冲实验中，胎儿型nAChR在应用ACh或SCH后从脱敏状态恢复快于成人型。在两种nAChRs上，SCH的脱敏恢复时间常数均慢于ACh。SCH 10um时与ACh 100um时的Tau_&lt；rec&gt；这些结果提示，SCH引起的神经肌肉阻滞是由于脱敏恢复速度较慢所致，成人型和胎儿型nAChR的不同导致了不同的脱敏状态。成人型nAChR对nAChRs竞争性拮抗剂维库溴铵的Ki值小于胎儿型。在维库溴铵或β-管库拉林存在下，重复加入和洗去ACh的顺序，两种nAChRs对ACh诱发电流的恢复均有显著差异，成人型反应减弱。这些结果表明，维库溴铵或β-管库拉林阻断通道的一部分是以非竞争性方式承担的，在成人型nAChR中这一比例似乎很大。

The effects of agonists and competitive antagonists on bovine muscle adult- (junctional) and fetal-type (extrajunctional) bovine muscle nicotinic acetylcholine receptors (nAChR) have been compared by using Xenopus oocyte expression system, and the following results were obtained.1. The Km values of the adult-type nAChR for acetylcholine (ACh) and succinyicholine (SCh) were not significantly different from those of the fetal-type The adult-type nAChR showed a faster time constant of current decay than the fetal-type did at 300 muM of ACh or SCh, when the currents were approximated by a single exponential function (p<0.05). At 1 mM, SCh exerted a potent blocking action of the open ion channel.2. In double pulse experiments, the recovery from the desensitized state after application of ACh or SCh was faster in the case of the fetal-type nAChR than in the adult-type. tau_<rec> (the time constant of recovery from desensitization) of SCh was slower than that of ACh on both nAChRs. tau_<rec> at 10 muM of SCh was almost the same as that at 100 muM of ACh. These results suggest that the neuromuscular blockade caused by SCh is due to the slow rate of recovery from desensitization and that the difference between adult- and fetal-type nAChR is responsible for different desensitized states.3. The Ki value of the adult-type nAChR for vecuronium, a competitive antagonist for nAChRs, was smaller than that of the fetal-type. When the sequence of addition and washout of ACh was repeated in the presence of vecuronium or beta-tubocurarine, both nAChRs showed remarkable difference in restoration of ACh- evoked currents and the adult-type showed the reduced response. These results suggest that a fraction of the channel blockade by vecuronium or beta-tubocurarine was borne in the non-competitive manner and the fraction appears to be large in the adult-type nAChR.