在通道中电压依赖性失活的分子决定因素
J F Zhang1, P T Ellinor, R W Aldrich
1Department of Molecular and Cellular Physiology, Stanford University Medical Center, California 94305.
Nature
|November 3, 1994
概括
研究人员确定了电压通道中的关键氨基酸,这些氨基酸负责失活动力学. 这一发现揭示了细胞过程中的通道功能和调节.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 生物物理学的生物物理.
背景情况:
- 电压依赖的通道 (Ca2+) 对于细胞信号发送至关重要,对膜去极化作出反应.
- 通道无活化,即开启后关闭的过程,对于调节Ca2+流入和下游细胞事件至关重要.
- 与和通道相比,对Ca2+通道不活化的分子机制的了解很少.
研究的目的:
- 为了阐明电压关闭通道失活的分子基础.
- 确定特定的区域和氨基酸,这些氨基酸决定了Ca2+通道失活的动力学.
主要方法:
- 构建嵌合式通道,通过将不同无活化率的通道段组合起来.
- 分析这些虚拟现象对通道失活动态的功能影响.
主要成果:
- 在α1子单元的第一个重复 (IS6) 的膜跨越段S6内的特定氨基酸是Ca2+通道失活动学的关键决定因素.
- 与IS6相邻的假定细胞外和细胞质域也会导致失活.
- 鉴定的区域不同于通道中的关键III-IV循环.
结论:
- Ca2+通道失活的分子决定因素局限于IS6区域及其侧面域.
- 这一发现为Ca2+通道功能的结构基础提供了新的见解.
- 2+通道不活性化与通道中观察到的C型不活性化有一些特征.
相关概念视频
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Voltage-gated Ion Channels
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...


