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相关概念视频

GPCR Desensitization01:12

GPCR Desensitization

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

2.0K
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...
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Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

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Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
1.4K
The Two-State Receptor Model01:29

The Two-State Receptor Model

1.8K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
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Opioid Receptors: Overview01:22

Opioid Receptors: Overview

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Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
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The Role of Ion Channels in Neuronal Computation01:19

The Role of Ion Channels in Neuronal Computation

3.1K
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....
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相关实验视频

Updated: May 13, 2025

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
11:19

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels

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结构洞察力到凯纳特受体脱敏化中的结构洞察力

Changping Zhou, Guadalupe Segura-Covarrubias, Nami Tajima

    bioRxiv : the preprint server for biology
    |April 16, 2025
    PubMed
    概括

    凯纳酸受体 (KARs) 在脱敏过程中经历独特的结构变化,与其他离子转移性谷氨酸受体 (iGluRs) 不同. 结构和功能数据显示,KAR联体结合域旋转对于完整的通道关闭和明显的脱敏机制至关重要.

    科学领域:

    • 神经科学是一个神经科学.
    • 结构生物学 结构生物学
    • 分子药理学分子药理学

    背景情况:

    • 凯纳酸受体 (KARs) 是离子型谷氨酸受体 (iGluRs),对中枢神经系统中激发性神经传递至关重要.
    • 受体脱敏调节突触传输强度和可塑性,但KAR脱敏机制与AMPA受体等其他iGluR不同.
    • 一个关键的未解决的问题是,为什么KARs需要大量的形状变化来使其脱敏,与AMPA受体对应物不同.

    研究的目的:

    • 阐明酸盐受体脱敏的独特机制和形态动力学.
    • 与其他IGluR相比,研究KAR中独特的脱敏感化过程的结构基础.
    • 了解带结合域 (LBD) 运动在KAR通道关口和孔隙关闭中的作用.

    主要方法:

    • 用冷电子显微镜 (cryo-EM) 来确定GluK2 KARs在非脱敏,浅脱敏和深脱敏状态中的结构.
    • 工程双氨酸突变和交叉连接被用来稳定特定的受体构造.
    • 进行了补丁电生理学和波动分析,以评估离子透性和脱敏化动力学.

    主要成果:

    • 冷EM结构揭示了多种KAR形状,包括一个浅层无敏状态,有不完全闭合的通道孔.
    • 工程交叉链稳定了KARs在类似AMPA受体脱敏的构造中,但保留了离子透性.

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    Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
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    Purification and Reconstitution of TRPV1 for Spectroscopic Analysis

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    Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
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    Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells

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    相关实验视频

    Last Updated: May 13, 2025

    Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
    11:19

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    Published on: July 4, 2016

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    Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
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    Purification and Reconstitution of TRPV1 for Spectroscopic Analysis

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    Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
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    Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells

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  • 电生理学数据显示,浅层无敏化KARs仍然具有导电性,这表明孔隙闭合不完全.

    • 结论:

    • 卡尔联体结合域的侧向旋转运动对于脱敏感化过程中完全关闭通道至关重要.
    • 这种巨大的形状变化使KAR脱敏性与其他iGluR不同,解释了它们独特的封闭性质.
    • 这项研究定义了KAR脱敏的独特机制和构造动态,进步了我们对突触传播的理解.