The V-ATPase is expressed in the choroid plexus and mediates cAMP-induced intracellular pH alterations

Henriette L Christensen, Teodor G Păunescu, Vladimir Matchkov, Dagne Barbuskaite, Dennis Brown, Helle H Damkier, Jeppe Praetorius

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The cerebrospinal fluid (CSF) pH influences brain interstitial pH and, therefore, brain function. We hypothesized that the choroid plexus epithelium (CPE) expresses the vacuolar H +-ATPase (V-ATPase) as an acid extrusion mechanism in the luminal membrane to counteract detrimental elevations in CSF pH. The expression of mRNA corresponding to several V-ATPase subunits was demonstrated by RT-PCR analysis of CPE cells (CPECs) isolated by fluorescence-activated cell sorting. Immunofluorescence and electron microscopy localized the V-ATPase primarily in intracellular vesicles with only a minor fraction in the luminal microvillus area. The vesicles did not translocate to the luminal membrane in two in vivo models of hypocapnia-induced alkalosis. The Na +-independent intracellular pH (pH i) recovery from acidification was studied in freshly isolated clusters of CPECs. At extracellular pH (pH o) 7.4, the cells failed to display significant concanamycin A-sensitive pH i recovery (i.e., V-ATPase activity). The recovery rate in the absence of Na + amounted to <10% of the pH i recovery rate observed in the presence of Na +. Recovery of pH i was faster at pH o 7.8 and was abolished at pH o 7.0. The concanamycin A-sensitive pH i recovery was stimulated by cAMP at pH 7.4 in vitro, but intraventricular infusion of the membrane-permeant cAMP analog 8-CPT-cAMP did not result in trafficking of the V-ATPase. In conclusion, we find evidence for the expression of a minor fraction of V-ATPase in the luminal membrane of CPECs. This fraction does not contribute to enhanced acid extrusion at high extracellular pH, but seems to be activated by cAMP in a trafficking-independent manner.

Artikelnummerno. e13072
TidsskriftPhysiological Reports
StatusUdgivet - 3 jan. 2017


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