The murine choroid plexus epithelium expresses the 2Cl-/H+-exchanger ClC-7 and Na+/H+ exchanger NHE6 in the luminal membrane domain

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The choroid plexus epithelium within the brain ventricles secretes the majority of the cerebrospinal fluid (CSF). The luminal Na+,K+-ATPase acts in concert with a host of other transport proteins to mediate efficient fluid secretion across the epithelium. The CSF contains little protein buffer, but the pH value seems nonetheless maintained within narrow limits, even when faced with acid/base challenges. The involvement of choroid plexus acid/base transporters in CSF pH regulation is highlighted by the expression of several acid/base transporters in the epithelium. The aim of the current study was to identify novel acid/base transporters expressed in the luminal membrane of the choroid plexus epithelium to pave the way for systematic investigations of each candidate transporter in the regulation of CSF pH. Mass spectrometry analysis of proteins from epithelial cells isolated by fluorescence activated cell sorting identified the Cl-/H+ exchangers ClC-3, -4, -5, and -7 in addition to known choroid plexus acid/base transporters. RT-PCR on FACS isolated epithelial cells confirmed the expression of the corresponding mRNAs, as well as NHE6 mRNA. Both NHE6 and ClC-7 were immunolocalized to the luminal plasma membrane domain of the choroid plexus epithelial cells. Dynamic imaging of intracellular pH and membrane potential changes in isolated choroid plexus epithelial cells demonstrated Cl- gradient-driven changes in intracellular pH and membrane potential that are consistent with Cl-/H+ exchange. In conclusion, we have detected for the first time NHE6 and ClC-7 in the choroid plexus, which are potentially involved in pH regulation of the CSF.

Original languageEnglish
JournalAmerican Journal of Physiology: Cell Physiology
Pages (from-to)C439-C448
Number of pages10
Publication statusPublished - Apr 2018

    Research areas

  • Journal Article, Choroid plexus, Intracellular pH, Acid-base transport, Cerebrospinal fluid, Mass spectrometry, Epithelial Cells/metabolism, Chloride Channels/genetics, Cerebrospinal Fluid/metabolism, Mice, Inbred C57BL, Male, Sodium-Hydrogen Exchangers/genetics, Animals, Flow Cytometry, Spectrometry, Mass, Electrospray Ionization, Membrane Potentials, Cell Membrane/metabolism, Proteomics/methods, Cell Separation/methods, Choroid Plexus/cytology, Hydrogen-Ion Concentration

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