Fig. 2. Ion composition and transport across the choroid plexus epithelial cells.

According to the classical hypothesis, ion transporters and channels in the choroid plexus epithelial cells account for the main part of cerebrospinal fluid (CSF) production. The apically expressed Na⁺/K⁺-ATPase, central to CSF secretion, creates the electrochemical gradient for Na⁺ that is imported via the Na⁺/H⁺ exchanger, NHE1 and/or the Na⁺-HCO₃^- co-transporter, NCBE in the basolateral membrane. Co-import of HCO₃^- via NCBE and hydration of CO₂ by carbonic anhydrase (C.A) increase the intracellular concentration of HCO₃^-, which creates an electrochemical gradient that drives the efflux of HCO₃^- via the basolateral-located Cl^-/HCO₃^- exchanger, AE2 and apical HCO₃^- channels. The operation of AE2 generates a rise in intracellular Cl^- driving the apical export of Cl^- through the NKCC1 and Cl^- channels. The final result of these processes at the choroid plexus epithelium is a net flux of Na⁺, HCO₃^- and Cl^- from the blood across the epithelium to the ventricles, which generates the osmotic gradient that makes water move through AQP1 thereby producing the CSF.