Chloride channel, CFTR

CFTR has a single-channel conductance of about 8 pS. It is present in the apical membranes of many epithelia. Its mutation leads to the potentially lethal disease cystic fibrosis. In addition to acting as a chloride channel, CFTR is also thought to regulate, e.g., the epithelial sodium channel ENaC, a molecularly unknown outwardly-rectifying chloride channel, and possibly also potassium channels and water channels. Some of these potential regulatory processes, however, are controversial. CFTR also acts as a receptor for bacteria. 

Defective chloride channel (CFTR) in epithelial cells leads to excessive mucus in lungs. 

O In CF, the cystic fibrosis transmembrane regulator (CFTR) chloride channel is dysfunctional and usually results in decreased chloride secretion and increased sodium absorption, leading to altered viscosity of fluid excreted by the exocrine glands and mucosal obstruction. 

The cystic fibrosis (cf) gene was first identified in 1989. It codes for CFTR, a 170 kDa protein that serves as a chloride channel in epithelial cells. Inheritance of a mutant cftr gene from both parents results in the cystic fibrosis phenotype. While various organs are affected, the most severely affected are the respiratory epithelial cells. These cells have, unsurprisingly, become the... 

Becq, F., M. D. Merten, M. A. Voelckel, M. Gola, and C. Figarella. 1993. Characterization of cAMP dependent CFTR-chloride channels in human tracheal gland cells. FEBS Lett 321 73-8. 

The majority of cases of cystic fibrosis result from deletion of phenylalanine at position 508 (AF508), which interferes with proper protein folding and the posttranslational processing of oligosaccharide side chains. The abnormal chloride channel protein (CFTR) is degraded by the cytosolic proteasome complex rather than being translocated to the cell membrane. Other functional defects in CFTR protein that teaches the cell membrane may also contribute to the pathogenesis of cystic fibrosis. 

CFTR (cystic fibrosis transmembrane conductance regulator) a membrane protein that functions as a chloride channel. 

The gene responsible for CF codes for the cystic fibrosis transmembrane conductance regulator (CFTR), which is a chloride channel expressed on the surface of epithelial cells that line the affected organs. 

To take a step closer to defining the function of DNA sequences, the sequences are fluorescence tagged to identify transcriptional activity of genes (but not translation of protein), which then can be related to the disease state or medication. This information allows researchers to hunt for genes that are affected in disease states (e.g., mutation in CFTR gene regulating a chloride channel in cystic fibrosis patients)... 

This issue of the journal has 11 reviews on the CFTR chloride channel, covering its structure, activity, regulation, biosynthesis, and pathophysiology. 

An alternatively spliced isoform may form chloride channels in heart.1 - As mentioned in Chapter 8, Section C,5 the CFTR protein is a member of the... 

ATP-dependent ABC transporter family. However, it is atypical because it also contains a regulated chloride channel) In secretory epithelia of intestines, pancreas, lungs, sweat glands, and kidneys Cl enters epithelial cells through their basolateral surfaces using an Na+ + K+ + 2 Cl cotransporter and exits the cells through their apical surfaces using the CFTR channel. Absorptive epithelia also contain both the cotransporter and the CFTR channel, but Cl flows into the cells from the exterior surface, and the distribution of the cotransporter and CFTR between basolateral and apical surfaces is opposite to that in secretory cells.1... 

Valero MS, Garay RP, Gros P, Alda JO. 2006. Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and Na-K-Cl cotransporter NKCC1 isoform mediate the vasorelaxant action of genistein in isolated rat aorta. Eur J Pharmacol 544 126-131. 

Cystic fibrosis is an autosomal recessive disease caused by mutations of the cystic fibrosis transmerobrane conductance regulator (CFTR) gene producing a dysfunctional chloride channel, normally located on the apical membrane of exocrine glands [16]. The disease manifests itself at an early age in the lung with accumulation of thick, sticky mucus and bacterial infections. These infections are followed by an inflammatory response, resulting in an Infiltration of neutrophils... 

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