通过一种涉及ATP的自克林机制,CFTR通过ATP的自克林机制调节向外调整的化物通道
E M Schwiebert1, M E Egan, T H Hwang
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cell
|June 30, 1995
概括
囊性纤维化转膜导电调节器 (CFTR) 通过释放ATP调节其他化物通道,然后激活这些通道. 这揭示了CFTR的一个新机制.
科学领域:
- 细胞生理学 细胞生理学
- 离子通道调节 离子通道调节
- 囊性纤维化研究研究
背景情况:
- 囊性纤维化跨膜导电调节器 (CFTR) 对于离子传输至关重要,但其在直接化物 (Cl-) 导电之外的作用尚不清楚.
- 虽然CFTR和外向纠正Cl-通道 (ORCC) 具有功能联系,但其调节机制仍然未知.
- 了解CFTR更广泛的调节功能是囊性纤维化病原体的关键.
研究的目的:
- 阐明CFTR调节其他离子通道的细胞机制.
- 调查CFTR和ORCC之间的功能联系.
- 确定CFTR是否通过其自身导电性以外的途径影响Cl-分泌.
主要方法:
- 在培养的呼吸道上皮细胞中进行全细胞和单通道补丁记录.
- 短路电流记录以测量离子传输.
- [gamma-32P]ATP释放试验测量细胞外ATP的数量.
- 使用正常,CF和CFTR转移细胞 (野生类型和突变细胞) 的实验.
主要成果:
- CFTR通过刺激细胞中的腺三酸盐 (ATP) 的释放来调节ORCC.
- 细胞外ATP通过P2U纯能受体依赖的信号通路激活ORCC.
- CFTR的功能超出了直接的Cl-运输范围,调节其他Cl-分泌通路.
结论:
- CFTR作为其他Cl-分泌通路的调节者,包括ORCCs.
- 由CFTR调解的ATP释放是一个关键的信号机制,将CFTR与ORCC激活联系起来.
- 这一发现扩大了CFTR已知的功能,并为囊性纤维化病理生理学提供了新的见解.
相关概念视频
pH Regulation in Cells
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
G-Protein Gated Ion Channels
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 organs,...
Sensory organs,...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Feedback 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...
Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
Reabsorption and Secretion in the DCT and Collecting Duct
The early phase of the DCT manages the reabsorption of approximately 10-15% of filtered water, 5–10% of filtered sodium, and 5–10% of filtered chloride. This process is facilitated by Na+–Cl− symporters in apical membranes and sodium-potassium pumps, as well as Cl− leakage channels in basolateral membranes. The early DCT also stands out as a site where parathyroid hormone (PTH) stimulates calcium reabsorption, depending on the body's requirements.
The distal part of the DCT, along with the...
The distal part of the DCT, along with the...


