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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Nhe1 is a luminal Na⁺/H⁺ exchanger in mouse choroid plexus and is targeted to the basolateral membrane in Ncbe/Nbcn2-null mice

¹Department of Anatomy, Aarhus University, Denmark; ²Department of Molecular Genetics, University of Cincinnati, Cincinnati, Ohio; and ³Department of Clinical Chemistry, Friedrich-Schiller-Universität Jena, Jena, Germany

Submitted 5 February 2009 ; accepted in final form 9 April 2009

The choroid plexus epithelium (CPE) secretes the major fraction of the cerebrospinal fluid (CSF). The Na⁺-HCO₃^– transporter Ncbe/Nbcn2 in the basolateral membrane of CPE cells is important for Na⁺-dependent pH_i increases and probably for CSF secretion. In the current study, the anion transport inhibitor DIDS had no effect on the residual pH_i recovery in acidified CPE from Ncbe/Nbcn2 knockout mouse by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-fluorescence microscopy in the presence of CO₂/HCO₃^– (Ncbe/Nbcn2-ko+DIDS 109% of control, P = 0.76, n = 5). Thus Ncbe/Nbcn2 mediates the DIDS-sensitive Na⁺-dependent pH_i recovery in the CPE. The Na⁺/H⁺ exchanger-1 Nhe1 is proposed to mediate similar functions as Ncbe/Nbcn2 in CPE. Here, we immunolocalize the Nhe1 protein to the luminal membrane domain in mouse and human CPE. The Na⁺-dependent pH_i recovery of Nhe1 wild-type (Nhe1-wt) mice in the absence of CO₂/HCO₃^– was abolished in the Nhe1 knockout CPE (Nhe1-ko 0.37% of Nhe1-wt, P = 0.0007, n = 5). In Ncbe/Nbcn2-ko mice, Nhe1 was targeted to the basolateral membrane. Nevertheless, the luminal Na⁺-dependent pH_i recovery was increased in Ncbe/Nbcn2-ko compared with wild-type littermates (Nhe1-ko 146% of Nhe1-wt, P = 0.007, n = 5). Whereas the luminal Nhe activity was inhibited by the Nhe blocker EIPA (10 µM) in the Ncbe/Nbcn2-wt, it was insensitive to the inhibitor in Ncbe/Nbcn2-ko (Ncbe/Nbcn2-ko+EIPA 100% of control, P = 0.98, n = 5). This indicates that a luminal EIPA-insensitive Nhe was induced in Ncbe/Nbcn2-ko CPE and that EIPA-sensitive Nhe activity was basolateral. The Nhe1 translocation in Ncbe/Nbcn2-ko CPE may reflect a compensatory response, which provides the cells with better means of regulating pH_i or transporting Na⁺ after Ncbe/Nbcn2 disruption.

membrane targeting; acid/base transporters; intracellular pH; immunohistochemistry

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				Highlights From the Literature Physiology, October 1, 2009; 24(5): 276 - 280. [Full Text] [PDF]