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1 The Water and Salt Research Center, University of Aarhus, Institute of Anatomy, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: jp{at}ana.au.dk.
The choroid plexus epithelium of the brain ventricular system produces the majority of the cerebrospinal fluid, and thereby defines the ionic composition of the interstitial fluid in the brain. The transepithelial movement of Na+ and water in the choroid plexus depend on a yet unidentified basolateral stilbene-sensitive Na+:HCO3- uptake protein. Reverse transcription - polymerase chain reaction (RT-PCR) analysis revealed the expression in the choroid plexus of SLC4A10 mRNA which encodes a stilbene-sensitive Na+:HCO3- transporter. Anti-c-terminal antibodies were developed to determine the specific expression and localization of this Na+:HCO3- transport protein. Immunoblotting demonstrated antibody binding to a 180 kDa protein band from mouse and rat brain preparations enriched with choroid plexus. The immunoreactive band migrated as a 140 kDa protein after N-deglycosylation, consistent with the predicted molecular size of the SLC4A10 gene product. Bright field immunohistochemistry and immunoelectron microscopy demonstrated strong labeling confined to the basolateral plasma membrane domain of the choroid plexus epithelium. Furthermore, the stilbene-insensitive Na+:HCO3- cotransporter, NBCn1, was also localized to the basolateral plasma membrane domain of the choroid plexus epithelium. Hence, we propose that the SLC4A10 gene product and NBCn1 both function as basolateral HCO3- entry pathways, and that the SLC4A10 gene product may be responsible for the stilbene-sensitive Na+:HCO3- uptake that is essential for cerebrospinal fluid production.
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