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在无氧神经元死亡中,TRPM7通道的关键作用
Michelle Aarts1, Koji Iihara, Wen-Li Wei
1Toronto Western Hospital Research Institute, 11-416 MC-PAV, 399 Bathurst Street, Toronto, Ontario M5T-2S8 Canada.
Cell
|December 31, 2003
概括
抗刺激性毒性疗法未能在缺血后预防脑损伤. TRPM7通道驱动神经元死亡,允许过载和反应性氧物种的产生,即使在治疗中.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 缺血性中风研究
背景情况:
- 兴奋毒性导致神经元死亡和脑缺血中的残疾.
- 目前的抗兴奋毒性疗法 (AET) 在人类临床环境中无效.
研究的目的:
- 调查大脑缺血中神经元死亡的潜在机制,这些机制没有被AET解决.
- 确定新的治疗点,以预防缺血性事件期间的细胞死亡.
主要方法:
- 在培养的神经元中利用氧气-葡萄糖剥夺 (OGD) 来模拟缺血状况.
- 研究了Ca2+透性非选择性阴离子导电 (IOGD) 和TRPM7通道的作用.
- 采用电生理学,成像和基因操纵 (TRPM7抑制).
主要成果:
- AET揭露了IOGD介导的占主导地位的死亡途径,由活性氧/物种 (ROS) 激活.
- 确定TRPM7道是IOGD的主要媒介,促进过载和ROS产生.
- 抑制TRPM7保护神经元免受无氧死亡,避免了对AET的需要.
结论:
- 兴奋毒性是更广泛的无氧细胞死亡机制的一个组成部分.
- TRPM7通道是脑缺血中神经元死亡的关键影响者.
- 准TRPM7为缺血性中风提供了一个有前途的治疗策略.
相关概念视频
The Resting Membrane Potential
Overview
Resting Membrane Potential
The relative difference in electrical charge, or voltage, between the inside and the outside of a cell membrane, is called the membrane potential. It is generated by differences in permeability of the membrane to various ions and the concentrations of these ions across the membrane.
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
The 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.
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...
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...
Resting Membrane Potential
The relative difference in electrical charge, or voltage, between the inside and the outside of a cell membrane, is called the membrane potential. It is generated by differences in permeability of the membrane to various ions and the concentrations of these ions across the membrane.
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...

