Stoichiometric analysis of the TM2 6' phenylalanine mutation on desensitization in alpha1beta2 and alpha1beta2gamma2 GABA A receptors.
Stoichiometric analysis of the TM2 6' phenylalanine mutation on desensitization in alpha1beta2 and alpha1beta2gamma2 GABA A receptors.
复制标题
TM2 6 苯丙氨酸突变对 alpha1beta2 和 alpha1beta2gamma2 GABA A 受体脱敏的化学计量分析。
DOI：
10.1016/j.neulet.2007.11.039
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发表时间：
2008
影响因子：
2.5
通讯作者：
Dillon,GlennH
中科院分区：
文献类型：
--
作者：
Gonzales,EricB;Bell-Horner,CathyL;Dibas,MohammedI;Huang,Ren-Qi;Dillon,GlennH
在α4β2烟碱受体α4亚基跨膜结构域2 （TM2）的6′位置存在苯丙氨酸(F)，增强了脱敏作用。由于gaba受体提供了研究少至1个，多至5个f在该位置的影响的能力，我们已经使用它来研究TM2 6'F突变对脱敏的潜在亚基和化学计量依赖效应。然而，在TM2 6′位置存在一个F会降低脱敏程度，而在TM2 6′位置包含两个或更多F的所有构型中，脱敏程度都有所增加；当存在3或4个F残基时，脱敏反应特别迅速。我们的研究结果表明，TM2 6 '位置的F残基调节脱敏的能力可能在配体门控离子通道的cys-loop家族中是保守的。此外，我们的研究结果表明，这种突变调节gaba受体脱敏的能力具有化学计量学和亚基依赖性。
The presence of phenylalanine (F) at the 6′ position of transmembrane domain 2 (TM2) in the α4 subunit of α4β2 nicotinic receptors enhances desensitization. As the GABAAreceptor affords the ability to study the influence of as few as one and as many as five Fs at this position, we have used it to investigate potential subunit- and stoichiometry-dependent effects of the TM2 6′F mutation on desensitization. Whereas the presence of one F at this position decreased extent of desensitization, desensitization was increased in all configurations that included two or more Fs at the TM2 6′ position; desensitization was particularly rapid with 3 or 4 F residues present. Our results demonstrate the ability of F residues at the TM2 6′ position to modulate desensitization is likely conserved in the cys-loop family of ligand-gated ion channels. Moreover, our findings demonstrate both stoichiometric- and subunit-dependent effects of the ability of this mutation to regulate desensitization in GABAAreceptors.