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#chloride channel

3 public questions tagged with this topic.

Membrane Transportation

Which ion transporter is defective in cystic fibrosis?

Cystic fibrosis is monogenic disease caused by dysfunction of chloride and bicarbonate channel CFTR, ABCC7, not by Na+/K+ ATPase primary gradient generator nor by V-type proton pump acidifying organelles nor by ABCB1 drug efflux pump. CFTR localized apically in respiratory epithelium, pancreatic ductules, sweat duct, intestinal crypts and male reproductive tract mediates cAMP-activated Cl- secretion driving fluid movement and maintaining airway surface liquid hydration and mucus viscosity. Loss-of-function reduces chloride and bicarbonate secretion, leads to thickened secretions, obstructive l

Ref: Riordan et al., Annu Rev Biochem 2008, CFTR and cystic fibrosis; Davies et al., Science 2023.

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Membrane Transportation

The ABC transporter CFTR is unique because:

CFTR ABCC7 stands as atypical member of ABC superfamily because evolution transformed an active exporter scaffold into ATP-gated ion channel. Typical ABC exporters use ATP binding and hydrolysis to drive large TMD movements translocating substrate uphill. In CFTR, transmembrane domains create chloride-selective pore allowing passive flow down electrochemical gradient when open, while nucleotide-binding domains still bind ATP and regulate gating rather than transport solute stoichiometrically. Two ATP sites: NBD1 non-canonical hydrolyzes slowly, NBD2 drives channel closure upon hydrolysis. Addi

Ref: Gadsby et al., Nature 2006, Unique CFTR channel mechanism; Hwang & Sheppard, 2009.

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Membrane Transportation

The CFTR transporter functions as a:

Cystic fibrosis transmembrane conductance regulator CFTR, ABCC7, is an exceptional ABC protein that functions not as active pump but as cAMP-activated chloride channel gated by ATP. It contains two transmembrane domains each with six helices forming chloride-selective pore, two nucleotide-binding domains, and a unique cytosolic R domain with multiple PKA phosphorylation sites. Channel opening requires R domain phosphorylation by protein kinase A downstream of adenylate cyclase, followed by ATP binding and NBD dimerization stabilizing open state; ATP hydrolysis at NBD2 terminates open burst. In

Ref: Gadsby et al., Nature 2006, CFTR gating cycle; Lodish, Molecular Cell Biology, CFTR chloride channel.

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