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

采用爪蟾卵母细胞表达系统，比较了激动剂和竞争拮抗剂对牛肌肉成体（结膜）和胎体（结膜外）牛肌肉烟碱乙酰胆碱受体（nAChR）的影响，得到了以下结果：成人型nAChR对乙酰胆碱（ACh）和琥珀酰胆碱（SCh）的Km值与胎儿型nAChR的Km值无显著差异，当电流用单指数函数近似时，成人型nAChR的电流衰减时间常数比胎儿型快（p<0.05）。在1mm时，SCh对开放离子通道发挥了有效的阻断作用。在双脉冲实验中，胎儿型nAChR在应用ACh或SCh后从脱敏状态恢复的速度要快于成人型。在两个nachr上，SCh的tau_<rec>（脱敏恢复时间常数）都比ACh慢。tau_<rec>在10 μ m的SCh作用下与100 μ m的ACh作用下几乎相同。这些结果表明，SCh引起的神经肌肉阻滞是由于脱敏恢复速度慢，而成人型和胎儿型nAChR的差异是不同脱敏状态的原因。成人型nAChR对竞争拮抗剂维库溴铵的Ki值小于胎儿型nAChR。在维库溴铵或β -管curarine存在的情况下，重复乙酰胆碱的添加和冲洗顺序，两种nachr对乙酰胆碱诱发电流的恢复有显著差异，成人型反应减弱。这些结果表明，维库溴铵或β -管库碱的一部分通道阻断是通过非竞争性方式进行的，并且在成体型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.