激活门动态和IFM图案在人类中的可访问性背后的结构和功能机制 Nav1.5
Rupam Biswas1, Ana Laura López-Serrano1,2, Apoorva Purohit3
1Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH, USA.
Nature communications
|February 16, 2026
概括
研究人员发现了电压通通道 (Nav1.5) 的一个新的中间开放状态. 这一发现揭示了离子结合如何影响通道功能,并可能导致心律障碍的新疗法.
科学领域:
- 结构生物学 结构生物学
- 分子生理学分子生理学
- 心血管研究研究心血管研究
背景情况:
- 电压通道 (Nav) 对于细胞的电活动至关重要.
- Nav通道的失调与各种疾病有关,包括心律失常.
- 针对Nav通道进行治疗是由于对其门机制的不完全理解而受到阻碍的.
研究的目的:
- 为了阐明 Nav1.5 门的结构基础.
- 调查中间开放状态在通道功能中的作用.
- 为开发Nav1.5向治疗提供一个框架.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定人类Nav的结构1.5.
- 分子动力学 (MD) 模拟来分析离子结合和通道动力学.
- 电生理学记录以评估结构发现的功能后果.
主要成果:
- 在中期开放状态下解决了Na1.5的新型冷-EM结构.
- 鉴定出了一个潜在的Na+结合位点,邻非活性化动机.
- 在这个部位的离子结合被证明可以调节无活化动力学和IFM动机对接.
- 证明了IFM可访问性在中间状态的动态调节.
结论:
- 这项研究完善了快速失活的正规门模型.
- 建议对Nav1.5门机制进行修订的结构框架.
- 这些发现表明离子可访问性的另一种途径,可能会为心律失常的治疗策略提供信息.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
4.2K
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...
4.2K
Mechanically-gated Ion Channels
7.9K
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...
7.9K
Ligand-gated Ion Channels
14.5K
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...
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...
14.5K
Non-gated Ion Channels
8.3K
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....
8.3K
The Role of Ion Channels in Neuronal Computation
3.9K
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....
3.9K
Voltage-gated Ion Channels
11.1K
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...
11.1K


