快速失活的神经元通道的功能表达
P T Ellinor1, J F Zhang, A D Randall
1Department of Molecular and Cellular Physiology, Stanford University Medical Center, California 94305.
Nature
|June 3, 1993
概括
研究人员对新型doe-1通道进行了表征,揭示它是一种高压激活通道,具有独特的无活化和药理特性,与其他已知的通道不同.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 离子通道生理学 离子通道生理学
背景情况:
- 多种通道 (T,N,L,P型) 在神经元中至关重要,将电活动与细胞功能联系起来.
- 大多数克隆的通道符合已建立的功能分类.
- 包括doe-1在内的通道基因家族的一个重要分支仍然在功能上没有表征.
研究的目的:
- 为了功能性地表征doe-1基因产物.
- 为了确定doe-1通道的电生理学和药理学特性.
- 在中枢神经系统中识别类似于doe-1的本源通道电流.
主要方法:
- 多伊-1.1的基因表达.
- 电生理学记录以评估通道功能.
- 使用特定的抗剂和毒素 (二皮里丁,欧米茄-Aga-IVA,欧米茄-CTx-GVIA,Ni2+) 的药理分析.
主要成果:
- doe-1编码了一个高压激活 (HVA) 通道.
- -1表现出快速无活化动力学,比以前研究的通道更快.
- 药理学分析揭示了新的特性:对二二和omega-Aga-IVA的耐药性,微分子度下omega-CTx-GVIA的可逆阻断,以及异常的Ni2+敏感性.
- 在老鼠大脑小粒神经元中存在的一种本源的Ca2+通道与doe-1具有动态和药理上的相似之处.
结论:
- doe-1代表了一种具有独特功能性质的HVA通道的新型类.
- -1的独特特征扩大了我们对神经元中的通道多样性和功能的理解.
- 已识别的本源电流表明了大脑中doe-1类通道的生理相关性.
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.
01:26Voltage-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...
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:30Ligand-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...
01:26Voltage-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...