对CLC-0从细胞内质子抑制的缓慢门的洞察
Hwoi Chan Kwon1, Robert H Fairclough1,2, Tsung-Yu Chen1,2,3
1Biophysics Graduate Program, University of California, Davis, CA 95618, USA.
International journal of molecular sciences
|July 27, 2024
概括
细胞内质子 (H+i) 通过关闭缓慢的门来抑制鱼雷CLC-0通道,这一过程类似于无活化. 穿过孔隙的阳离子流加快了慢门的打开速度,揭示了多个不活化的状态.
科学领域:
- 分子生物学分子生物学
- 离子通道生理学 离子通道生理学
- 生物物理学的生物物理.
背景情况:
- 鱼雷CLC-0化物通道关门涉及快速和缓慢的机制.
- 慢门机制的结构基础仍然不太清楚.
- 之前的工作与细胞内质子 (H+i) 抑制与缓慢关闭 (非激活) 相关.
研究的目的:
- 进一步阐明野生型CLC-0和突变道中H+i抑制的机制.
- 调查阴离子流出在H+i诱导的抑制后恢复中的作用.
- 探索CLC-0通道中非活化状态的性质.
主要方法:
- 野生类型和突变CLC-0通道的电生理记录.
- 细胞内质子 (H+i) 的应用来诱导通道抑制.
- 在各种条件下分析当前回收动力学,包括离子流量.
- 使用非激活抑制突变物来探测通道状态.
主要成果:
- 通过CLC-0孔的阳离子流出加速了H+i诱导的抑制的恢复,这表明缓慢的门打开.
- 被非激活抑制的突变体表现出不同的当前恢复动力学,这表明多个慢门关闭 (非激活) 状态.
- +i可能会增加孔中的离子结合亲和力,引发孔堵塞和随后的无活化.
结论:
- H+i诱导的CLC-0通道的抑制涉及缓慢的门关闭,与非激活一致.
- 阳离子透有助于缓慢打开门,逆转H+i诱导的抑制.
- 多个无活化状态的存在得到了突变体中差异性恢复动力学的支持.
相关概念视频
Ligand-gated Ion Channels
12.3K
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...
12.3K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
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...
2.2K
ATP Driven Pumps I: An Overview
8.0K
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and...
8.0K
G-Protein Gated Ion Channels
4.6K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.6K
Patch Clamp
5.4K
Many fundamental cell functions such as muscle contraction and nerve transmission rely on the electrical signals produced by the movement of positively and negatively charged ions across the cell membrane. One competent method to record current flowing across the whole cell or single ion channel is the patch-clamp technique.
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
5.4K
Secondary Active Transport
7.0K
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
7.0K


