Serum choline activates mutant acetylcholine receptors that cause slow channel congenital myasthenic syndromes.
Serum choline activates mutant acetylcholine receptors that cause slow channel congenital myasthenic syndromes.
复制标题
血清胆碱激活突变的乙酰胆碱受体，导致慢通道先天性肌无力综合征。
DOI：
10.1073/pnas.96.18.10466
复制
发表时间：
1999
影响因子：
11.1
通讯作者：
Auerbach,A
中科院分区：
文献类型：
--
作者：
Zhou,M;Engel,AG;Auerbach,A
我们发现，引起慢通道先天性肌无力综合征的突变型乙酰胆碱受体通道(AChRs)由血清激活，血清中高频率的开放可通过胆碱氧化酶处理而减少。因此，神经肌肉交界处的慢通道先天性肌无力综合征AChRs很可能通过稳定暴露于血清胆碱和短暂暴露于突触释放的递质而激活。单通道动力学分析表明，对胆碱的反应增强是由于闭合通道的固有稳定性降低所致。结果表明，破坏AChR非活性构象稳定的突变，加上终板持续暴露于血清胆碱，导致持续的通道活动，从而促进了疾病的病理生理。
We have found that mutant acetylcholine receptor channels (AChRs) that cause slow-channel congenital myasthenic syndromes are activated by serum and that the high frequency of openings in serum is reduced by treatment with choline oxidase. Thus, slow-channel congenital myasthenic syndrome AChRs at the neuromuscular junction are likely to be activated both by steady exposure to serum choline and by transient exposure to synaptically released transmitter. Single-channel kinetic analyses indicate that the increased response to choline is caused by a reduced intrinsic stability of the closed channel. The results suggest that a mutation that destabilizes the inactive conformation of the AChR, together with the sustained exposure of endplates to serum choline, results in continuous channel activity that contributes to the pathophysiology of the disease.