The choroid plexus regulation of cerebrospinal fluid pH

Abstract

The choroid plexus epithelium (CPE) lines the ventricular spaces of the brain and secretes the majority of the cerebrospinal fluid (CSF). Changes in blood pCO2 are efficiently transmitted to the CSF, which lack protein buffers. Nevertheless, the CSF pH fluctuates significantly less than would be predicted from the pCO2 changes. This ascertains a proper respiratory center response.Despite the clear clinical importance, strikingly little is known about the molecular mechanisms behind CSF pH control. The aim of this study is to determine whether the CPE is involved in CSF pH regulation.As a first step, we wished to identify the types of putative pH, HCO3− or CO2 sensor proteins and luminal acid‐base extruders expressed in the CPE. RT‐PCR on mouse choroid plexus revealed mRNA encoding the sensor proteins TDAG8, OGR1, Gpr4, Ptprg, and sAC. We have also demonstrated mRNA expression of the putative luminal acid‐base extruders NHE1 and NBCe2, as well as the A, B2, C1, C2, d1 and d2 subunits of the vacuolar H+‐ATPase (V‐ATPase). NHE1 and NBCe2 are known luminal proteins in the CPE, while preliminary immunolocalization of the V‐ATPase suggests a mainly vesicular distribution.In conclusion, the CPE expresses a molecular machinery that may well confer both acid‐base sensing and potent transport capacity to regulate CSF pH within suitable limits.