The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates cerebrospinal fluid pH
Research output: Contribution to journal › Conference abstract in journal › Research › peer-review
Respiratory centers in the central nervous system (CNS) react to changes in pCO2 and maintain systemic acid/base homeostasis by controlling the rate and depth of respiration. Both blood-brain barrier and blood-CSF barrier are highly permeable to CO2 enabling swift transmission of arterial pCO2 fluctuations to be coupled with CSF pH changes, whilst both barriers are much less permeable to H+ and HCO3−, hence masking the effects of metabolic acid-base disturbances. The electrogenic Na+-HCO3− cotransporter NBCe2 is expressed in the CSF-facing plasma membrane of the choroid plexus epithelial (CPE) cells and could be a regulator of CSF pH. We hypothesized that NBCe2 is responsible for HCO− extrusion into the ventricle lumen to counteract decreases in CSF pH during acidosis. Intracellular pH (pHi) measurements on CPE cells from NBCe2 knockout (KO) mice showed a statistically significant 84% increase in Na+-dependent acid extrusion following intracellular acidification by ammonium chloride prepulse and an 81% reduction in DIDS-sensitive base efflux after intracellular alkalization by trimethylamine. Knockout of NBCe2 abolished CSF pH recovery from hypercapnia-induced acidosis compared to control mice: wt (n=5): 0.0048 ± 0.003 vs ko (n=6): −0.0001±0.0002 pH units/min, p=0.0043. Choroid plexus targeted NBCe2 knockdown mice generated by intracerebroventricular installation of siRNA revealed a similar effect: Control (n=5): 0.002+/−0.0004 vs. NBCe2 knockdown (n=7): −0.0001±0.0007, p=0.047. Knockout of NBCe2 did not affect respiration rate or tidal volume compared to wildtype, and revealed a similar ventilatory response as controls when exposed to 5% CO2. In conclusion, we show that NBCe2 is important for recovery of CSF pH after CO2 induced acidosis by transporting HCO3− into the CSF. This suggests a significant role for NBCe2 in regulating brain pH when faced with an acid challenge independent of the respiratory response.
Original language | English |
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Article number | 702.4 |
Journal | F A S E B Journal |
Volume | 31 |
Issue number | S1 |
Number of pages | 1 |
ISSN | 0892-6638 |
Publication status | Published - 2017 |
Links
- http://www.fasebj.org/content/31/1_Supplement/702.4.short
Final published version
ID: 183610627