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Nhe1 is a luminal protein in the mouse choroid plexus epithelium that translocates to the basolateral surface in Ncbe‐null mice
Author(s) -
Praetorius Jeppe,
Hübner Christian A,
Damkier Helle H
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.799.1
Subject(s) - amiloride , sodium–hydrogen antiporter , choroid plexus , epithelial sodium channel , epithelial polarity , chemistry , apical membrane , microbiology and biotechnology , medicine , acetazolamide , homeostasis , endocrinology , sodium , biology , biochemistry , membrane , organic chemistry , central nervous system
The choroid plexus epithelium, CPE, secretes a major fraction of the cerebrospinal fluid, CSF. The Na + ;HCO 3 − transporter, Ncbe/Nbcn2, in the basolateral membrane of CPE cells is important for Na + dependent pH i increases and probably for CSF secretion. The Na + /H + exchanger‐1, Nhe1, have been proposed to mediate similar functions in CPE. Nhe1 protein was immunolocalized to the luminal membrane domain in CPE and was absent in CPE from Nhe1 knockout, ko, littermates. The Na + ‐dependent pH i recovery in the absence of CO 2 /HCO 3 − was dramatically decreased in the Nhe1‐ko mice compared to Nhe1‐wild type, wt, (ko 1.55% of wt, n=6, p=0.02) by fluorescence microscopy. In Ncbe‐ko mice, immunoreactive Nhe1 was targeted to the basolateral membrane, but luminal Na + dependent pH i recovery was in fact increased in Ncbe‐ko compared to wt littermates (ko 146.1% of wt, n=5, p=0.007). In Ncbe‐wt mice, the luminal Nhe activity was expectedly inhibited by the Nhe blocker, 5′‐(N‐ethyl‐N‐isopropyl)‐amiloride (EIPA, 10µM), while in Ncbe‐ko, Nhe activity was insensitive to the inhibitor (ko 939.0% of wt, n=5, p=0.036). This indicates that a luminal, EIPA‐insensitive Nhe was induced and that EIPA‐sensitive Nhe activity was basolateral in Ncbe‐ko CPE. We speculate that the Nhe1 translocation in Ncbe‐ko CPE reflects a compensatory response, which provides the cells with better means of regulating pH i in the absence of Ncbe.