人类与大脑功能障碍相关的P/Q型通道
A Jouvenceau1, L H Eunson, A Spauschus
1University Department of Clinical Neurology, Institute of Neurology, University College London, Queen Square, WC1N 3BG, London, UK.
Lancet (London, England)
|September 21, 2001
概括
影响P/Q型通道的CACNA1A基因突变与人类的缺席和动脉有关. 这一发现揭示了这些神经系统疾病的遗传原因.
科学领域:
- 神经遗传学 神经遗传学
- 分子神经科学 分子神经科学
背景情况:
- 常见的中枢神经系统疾病的遗传基础,包括,往往是未知的.
- 在动物模型中,P/Q型电压通道的突变会导致缺席和缺氧.
研究的目的:
- 为了研究P/Q型电压通道 (CACNA1A) 在患有和偶发性性动力衰竭的患者中的作用.
- 为了确定与复杂的神经现象型相关的CACNA1A中的遗传突变.
主要方法:
- 在一个11岁的患者中测序CACNA1A基因,该患者患有普遍性和渐进性性无氧.
- 引入已识别的突变进入子cDNA用于电生理表达研究.
- 对突变和野生类型通道功能和共同表达效应的分析.
主要成果:
- 在CACNA1A中发现了一种新型异构点突变 (C5733T),导致过早停止子 (R1820stop).
- 这种突变导致通道子单元的C端区域丧失.
- 电生理学研究证实了通道功能受损和主导负效应.
结论:
- 人类缺席可能是由大脑P/Q型电压通道功能障碍引起的.
- 患者的表型与与CACNA1A突变相关的缺席的小鼠模型非常相似.
相关概念视频
Gap Junctions
Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
Aquaporins
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.
Non-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.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Non-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.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Ligand-Gated Ion Channel Receptor: Gating Mechanism
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...


