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 lung disease with chronic Pseudomonas infection, pancreatic insufficiency, meconium ileus, and elevated sweat chloride above 60 mmol/L diagnostic hallmark. More than 2000 mutations including F508del, G551D, R117H impair trafficking, gating or conductance. Therapeutic correctors and potentiators target CFTR directly. Na+/K+ ATPase generates electrochemical gradient consumed by secondary transporters, V-ATPase acidifies lysosomes, ABCB1 effluxes xenobiotics, none cause hallmark multisystem chloride transport defect seen in cystic fibrosis. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.
Ref: Riordan et al., Annu Rev Biochem 2008, CFTR and cystic fibrosis; Davies et al., Science 2023.