Campos-Caro A, Rovira J C, Vicente-Agulló F, Ballesta J J, Sala S, Criado M, Sala F
Departamento de Neuroquímica, Universidad de Alicante, Spain.
Biochemistry. 1997 Mar 4;36(9):2709-15. doi: 10.1021/bi9623486.
The involvement of some structural domains in the gating of the neuronal nicotinic acetylcholine receptor (AChR) was studied by expressing functional alpha7/alpha3 chimeric subunits in Xenopus oocytes. Substitution of the M3 transmembrane segment in the alpha7 subunit modifies the kinetic properties of the chimeric AChRs as follows: (a) a 6-fold reduction in the maximal current evoked by nicotinic agonists, (b) a 10-fold decrease in the macroscopic desensitization rate, (c) an increase of almost 1 order of magnitude in the apparent affinity for acetylcholine and nicotine, and (d) a decrease in the affinity for alpha-bungarotoxin. Computer simulations showed that the first three effects could be accounted for by a simple kinetic model in which chimeric AChRs presented a smaller ratio of the gating rates, beta/alpha, and a slightly slower desensitization rate. It is concluded that the M3 domain influences the gating of neuronal AChRs.
通过在非洲爪蟾卵母细胞中表达功能性α7/α3嵌合亚基，研究了一些结构域在神经元烟碱型乙酰胆碱受体（AChR）门控中的作用。α7亚基中M3跨膜片段的替换对嵌合型AChR的动力学特性产生如下影响：（a）烟碱型激动剂诱发的最大电流降低6倍；（b）宏观脱敏速率降低10倍；（c）对乙酰胆碱和尼古丁的表观亲和力增加近1个数量级；（d）对α-银环蛇毒素的亲和力降低。计算机模拟表明，前三种效应可以用一个简单的动力学模型来解释，在该模型中，嵌合型AChR呈现出较小的门控速率比β/α，且脱敏速率略慢。得出结论：M3结构域影响神经元AChR的门控。
