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1 Inst. for Physiology and Biophysics, University of Aarhus, Ole Worms alle 1160, Aarhus, 8000, Denmark,
2 Water and Salt Research Center, University of Aarhus, Aarhus, 8000, Denmark,
3 Inst. of Anatomy, University of Aarhus, Wilhelm Meyers Alle 1233/1234, Aarhus, 8000, Denmark
ABSTRACT
Cerebrospinal fluid (CSF) is produced with a rate of about 3.4 µl/min in rats (Chodobski et al., 1998) of which the majority is secreted by the choroid plexus epithelium (CP) in the four brain ventricles. The apically localized Na+/K+ ATPase mediates the Na+ secretion and the driving force for the less well established basolateral Na+ uptake into the CP cells. The involvement of Na+/H+ exchange (NHE) in CP-mediated CSF formation has been suggested previously but NHE proteins have not been detected. Thus, we aimed to investigate the importance of bicarbonate independent Na+ uptake in intracellular pH regulation in CP using an intracellular fluorescent pH indicator. Amiloride (600 µM), EIPA (50 µM), HOE 694 (10 µM) were used to block NHE. Experiments on enzymatically isolated cells revealed Na+ dependent pHi recovery in the absence of HCO3/CO2 that was sensitive to amiloride (600 µM), whereas the more specific NHE1 blockers EIPA (50 µM), HOE 694 (10 µM) had no effect on pHi recovery. The mRNA encoding NHE1 and NHE8 was detected in rat CP, and at least NHE1 also in an isolated epithelial preparation. The results suggest that Na+/H+ exchange in CP may be mediated by NHE1, although the relative insensitivity to NHE inhibitors may suggest the involvement of another NHE. In conclusion, NHE proteins can not be excluded as basolateral Na+ entry mechanisms in CP-mediated CSF secretion.
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