在K+通道中缓慢失活后的恢复由水分子控制
Jared Ostmeyer1, Sudha Chakrapani, Albert C Pan
1Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E57th Street, Chicago, Illinois 60637, USA.
Nature
|July 30, 2013
概括
埋藏的水分子将 (K+) 通道在非导电状态中进行绝缘锁定. 正如KcsA通道模拟中所示,释放这些水分子解释了缓慢的恢复,并且可以通过透应激加速.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 离子通道生理学 离子通道生理学
背景情况:
- (K+) 通道调节细胞膜间的离子运输,对细胞功能至关重要.
- 在原子层面上,通道无活化和恢复机制仍然不完全理解.
- 细菌的KcsA通道提供了一个模型系统,可以在没有电压感应域的情况下研究这些过程.
研究的目的:
- 阐明K+通道失活缓慢恢复的基础的原子层次机制.
- 研究内部水分子在维护KcsA通道无活化状态中的作用.
- 开发一种解释K+通道恢复时间尺度的动力模型.
主要方法:
- 对KcsA通道的长分子动力学模拟.
- 潜在的平均力 (PMF) 计算来评估能源景观.
- 基于模拟数据的动力建模.
- 使用透应激 (2M糖糖) 的实验验证.
主要成果:
- 识别了埋藏的水分子,在非激活状态下,它们会使选择性过器受到硬质性阻碍.
- 证明这些水分子的释放是缓慢恢复过程中的关键因素.
- PMF计算揭示了水分子和外部K+离子对恢复动力学的影响.
- 模拟预测,减少水占用率可以加速恢复.
结论:
- 埋藏的水分子在干净锁定KcsA通道在其无活化的构造中发挥着至关重要的作用.
- 这些水分子的释放决定了通道恢复的缓慢,多秒的时间表.
- 透应激通过加速恢复率来实验验证模拟结果.
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相关概念视频
01:19The Role of Ion Channels in Neuronal Computation
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
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Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
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01:15Resting Potential Decay
The resting membrane potential of a neuron (-70mV) is sustained due to the selective ion permeability of the membrane. At the resting potential, the membrane is slightly permeable to ions like sodium (Na+) and chloride (Cl−) and highly permeable to potassium ions (K+). Differences in the ions' concentration inside the cell compared to the outside are maintained by membrane transport proteins like channels and pumps.
At rest, the K+ is the main ion that moves across the membrane through...
At rest, the K+ is the main ion that moves across the membrane through...
01:15Resting Potential Decay
The resting membrane potential of a neuron (-70mV) is sustained due to the selective ion permeability of the membrane. At the resting potential, the membrane is slightly permeable to ions like sodium (Na+) and chloride (Cl−) and highly permeable to potassium ions (K+). Differences in the ions' concentration inside the cell compared to the outside are maintained by membrane transport proteins like channels and pumps.
At rest, the K+ is the main ion that moves across the membrane through...
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Aquaporins or AQPs are a family of integral membrane proteins whose primary function is to transport water, while some called aquaglyceroporins also transport glycerol. In addition, aquaporins have also been suspected to be involved in transporting volatile substances, such as carbon dioxide and ammonia, across membranes. Such AQPs that act as gas channels are often highly expressed in cells involved in the gaseous exchange, such as red blood cells, epithelial cells, and pulmonary capillaries.