プラズマ膜のNa+/Ca2+交換器の割れは,興奮毒性において
Daniele Bano1, Kenneth W Young, Christopher J Guerin
1MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road LE1 9HN, Leicester, United Kingdom.
Cell
|February 1, 2005
まとめ
脳のイシュケミア中のナトリウム-カルシウム交換器 (NCX) のプロテオリチク割れは,カルシウム過負荷とニューロン死亡を引き起こす. この分裂を阻害すると,神経細胞が興奮毒性から救われ,NCX不活性化が脳損傷の重要なメカニズムであることを明らかにします.
科学分野:
- 神経科学は神経科学である.
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- 脳缺血と興奮毒性は,細胞内カルシウム過負荷によるニューロン死亡につながる.
- グルタミン酸受容体は,神経細胞へのカルシウム流入を調節する上で重要な役割を果たします.
研究 の 目的:
- Na+/Ca2+交換器 (NCX) が脳イシュケミアおよび興奮毒性におけるニューロンカルシウム脱調における役割を調査する.
- NCXのプロテオリスティック無活性化が興奮毒性ニューロン死亡に寄与するかどうかを判断する.
主な方法:
- 脳不全と興奮毒性状態におけるNCXの分裂を研究した.
- カルパスタチンの過剰発現とsiRNA媒介のNCXのダウンレギュレーションを利用してNCXの活性を調節した.
- 細胞内Ca2+レベルとニューロン生存率の評価.
主要な成果:
- Na+/Ca2+交換器 (NCX) は,脳イシュケミアおよびエキシト毒性において,タンパク質分解により分裂する.
- カルパイン媒介によるNCX分裂の抑制により,Ca2+過負荷が防止され,ニューロンが救助されました.
- NCXのダウンレギュレーションは,Ca2+の過剰負荷とニューロン死亡を悪化させた.
結論:
- Na+/Ca2+交換器 (NCX) のタンパク質分解性無活性化 (Proteolytic inactivation) は,遅延したカルシウム脱調と興奮毒性におけるニューロンの死を引き起こす重要なメカニズムである.
- NCXの割れ目をターゲットにすることは,脳イシュケミアおよび関連する神経学的疾患に対する潜在的な治療戦略です.
関連する概念動画
01:21The Resting Membrane Potential
117.6K
Overview
117.6K
01:24Resting Membrane Potential
18.4K
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...
18.4K
01:26Voltage-gated Ion Channels
11.2K
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...
11.2K
01:26Chemical Synapses
9.5K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
9.5K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
4.6K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
4.6K
01:26Chemical Synapses
10.9K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
10.9K