MOLECULAR DETERMINANTS OF ACETYLCHOLINE RECEPTOR GATING

乙酰胆碱受体门控的分子决定因素

• 批准号: 6394967
• 负责人: Steven M Sine
• 金额: $ 4.04万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394967
• 关键词: acetylcholine; chemical kinetics; electrophysiology; gene mutation; isoleucine; leucine; membrane channels; membrane structure; mutant; neural transmission; neurotransmitter receptor; nicotinic receptors; protein structure function; receptor expression; site directed mutagenesis; striated muscles; tissue /cell culture; valine; voltage /patch clamp

Neurotransmitter-gated ion channels mediate synaptic transmission throughout the nervous system. The nicotinic acetylcholine receptor (AChR) from skeletal muscle has served as a prototype for understanding the members of the superfamily of receptors, which includes neuronal nicotinic, glycine, GABAA, and 5-HT3 receptors. The essential function of this class of proteins is to transduce neurotransmitter binding into opening of an intrinsic ion channel. To better understand how neurotransmitter-gated ion channels function, the work proposed in this application will identify amino acids in transmembrane domains of the AChR that govern rates of opening and closing of the channel. The approach combines site-directed mutagenesis of residues in transmembrane domains and expression in mammalian cells with single channel recording and kinetic analysis. The overall findings will relate transmembrane domain structure to elementary steps underlying gating of the AChR channel.

神经递质门控离子通道介导整个神经系统的突触传递。 来自骨骼肌的烟碱乙酰胆碱受体（AChR）已用作理解受体超家族成员的原型，所述受体超家族成员包括神经元烟碱、甘氨酸、GABAA和5-HT 3受体。 这类蛋白质的基本功能是将神经递质结合到内在离子通道的开放中。 为了更好地了解神经递质门控离子通道的功能，本申请中提出的工作将确定AChR跨膜结构域中的氨基酸，这些氨基酸控制通道的开放和关闭速率。 该方法将跨膜结构域中残基的定点诱变和哺乳动物细胞中的表达与单通道记录和动力学分析相结合。 总体研究结果将跨膜结构域的基本步骤门控乙酰胆碱受体通道。

项目成果

The noncompetitive inhibitor quinacrine modifies the desensitization kinetics of muscle acetylcholine receptors.

非竞争性抑制剂奎纳克林改变肌肉乙酰胆碱受体的脱敏动力学。

• DOI: 10.1124/mol.60.2.235
• 发表时间: 2001
• 期刊: Molecular pharmacology
• 影响因子: 3.6
• 作者: Spitzmaul,G;Dilger,JP;Bouzat,C
• 通讯作者: Bouzat,C

Mechanistic contributions of residues in the M1 transmembrane domain of the nicotinic receptor to channel gating.

烟碱受体 M1 跨膜结构域中残基对通道门控的机制贡献。

• DOI: 10.1080/09687680310001607341
• 发表时间: 2004
• 期刊: Molecular membrane biology.
• 作者: Spitzmaul,Guillermo;Corradi,Jeremias;Bouzat,Cecilia
• 通讯作者: Bouzat,Cecilia

Nicotinic receptor M3 transmembrane domain: position 8' contributes to channel gating.

烟碱受体 M3 跨膜结构域：位置 8 有助于通道门控。

• DOI: 10.1124/mol.62.2.406
• 发表时间: 2002
• 期刊: Molecular pharmacology
• 影响因子: 3.6
• 作者: DeRosa,MaríaJosé;Rayes,Diego;Spitzmaul,Guillermo;Bouzat,Cecilia
• 通讯作者: Bouzat,Cecilia

The anthelmintic pyrantel acts as a low efficacious agonist and an open-channel blocker of mammalian acetylcholine receptors.

驱虫药噻嘧啶是一种低效激动剂和哺乳动物乙酰胆碱受体的开放通道阻断剂。

• DOI: 10.1016/s0028-3908(01)00057-0
• 发表时间: 2001
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Rayes,D;DeRosa,MJ;Spitzmaul,G;Bouzat,C
• 通讯作者: Bouzat,C