两孔的K+通道TREK-1调节压力过载引起的心脏重塑
Cemantha M L Johnson1,2, Drew M Nassal1,3, Alexander J Winkle1,2
1Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
概括
两孔通道TREK-1在心力衰竭中起着复杂的作用. 虽然缺少它会使心脏重塑和电气不稳定性恶化,但TREK-1在这种情况下也表现出保护作用.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 心力衰竭 (HF) 是一个重要的医疗负担,与心室心律不整的风险增加有关.
- 在高频中驱动结构和电气改造的机制尚未完全理解.
- 两孔K+通道TREK-1在心脏重塑中的作用需要阐明.
研究的目的:
- 调查TREK-1在压力过载诱导的高压心脏病期间心脏重塑中的作用.
- 确定TREK-1缺乏如何影响心脏功能,电活动和细胞信号传输.
主要方法:
- 心脏特异性TREK-1条件淘汰 (TREK1cKO) 和对照小鼠经历了心经狭窄 (TAC) 或假冒程序.
- 用心声图和心电图来评估心脏功能和电活动.
- 对心室肌细胞进行了动作潜力,细胞内Ca2+和收缩性分析;评估了关键细胞信号通路.
主要成果:
- 无论是TREK1cKO还是对照小鼠,都显示TAC后心功能下降和高.
- 与对照组相比,TREK1cKO小鼠表现出更严重的功能衰退和左心室扩张的增强.
- TAC TREK1cKO小鼠表现出延长的QT和QRS间隔,心室肌细胞显示出动作潜力的延长和矛盾的Ca2+平衡改善.
结论:
- TREK-1 缺陷加剧了心脏功能障碍和压力过载引起的高频电流中的电气异常.
- TREK-1 影响STAT3 酸化,表明与这种信号通路的复杂相互作用.
- 在心脏重塑过程中,TREK-1 具有不适应性和保护性作用,突出显示了它在心脏衰竭病理生理学中的复杂作用.
相关概念视频
01:24Non-gated Ion Channels
6.6K
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....
6.6K
01:32Secondary Active Transport
6.7K
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...
6.7K
01:27ATP Driven Pumps I: An Overview
7.8K
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...
7.8K
01:34ATP Driven Pumps II: P-type Pumps
4.4K
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
4.4K
01:18Patch Clamp
5.3K
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...
5.3K
01:44The Significance of Membrane Transport
21.0K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
21.0K