Identification and properties of a novel variant of NBC4 (Na+/HCO3− co-transporter 4) that is predominantly expressed in the choroid plexus

2013 ◽  
Vol 450 (1) ◽  
pp. 179-187 ◽  
Author(s):  
Hidekazu Fukuda ◽  
Taku Hirata ◽  
Nobuhiro Nakamura ◽  
Akira Kato ◽  
Katsumasa Kawahara ◽  
...  

Secretion of HCO3− at the apical side of the epithelial cells of the choroid plexus is an essential step in the formation of cerebrospinal fluid. Anion conductance with a high degree of HCO3− permeability has been observed and suggested to be the major pathway for HCO3− transport across the apical membrane. Recently, it was found that NBC (Na+/HCO3− co-transporter) 4, an electrogenic member of the NBC family, was expressed in the choroid plexus. We found that a novel variant of the NBC4 [NBC4g/Slc4a5 (solute carrier family 4, sodium bicarbonate co-transporter, member 5)] is almost exclusively expressed in the apical membrane of rat choroid plexus epithelium at exceptionally high levels. RNA interference-mediated knockdown allowed the functional demonstration that NBC4g is the major player in the HCO3− transport across the apical membrane of the choroid plexus epithelium. When combined with a recent observation that in choroid plexus epithelial cells electrogenic NBC operates with a stoichiometry of 3:1, the results of the present study suggest that NBC4g mediates the efflux of HCO3− and contributes to cerebrospinal fluid production.

2019 ◽  
Vol 99 (8) ◽  
pp. 1245-1255 ◽  
Author(s):  
Alexa N. Lauer ◽  
Martin März ◽  
Svenja Meyer ◽  
Marita Meurer ◽  
Nicole de Buhr ◽  
...  

1977 ◽  
Vol 199 (1135) ◽  
pp. 321-326 ◽  

Choroid plexuses from early (30–60 days gestation) and late (125 days) sheep foetuses were examined by various ultrastructural techniques in order to investigate possible explanations for the greater penetration of protein and non-electrolytes from blood into cerebrospinal fluid (c. s. f.), which occurs in the early foetus in contrast to later stages. The greater penetration occurs despite the presence of well-formed tight junctions between the epithelial cells and the development of some of the characteristic ion gradients between c. s. f. and plasma. A tubulocisternal system of endoplasmic reticulum appears to connect the basolateral and the apical cell surfaces in the early but not in the late foetuses. Several types of connection between the endoplasmic reticulum and the cell membrane were present in the early foetuses; these may account for some of the different permeability properties of the immature choroid plexus.


2020 ◽  
Vol 21 (19) ◽  
pp. 7230
Author(s):  
Yoichi Chiba ◽  
Ryuta Murakami ◽  
Koichi Matsumoto ◽  
Keiji Wakamatsu ◽  
Wakako Nonaka ◽  
...  

The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases.


2017 ◽  
Vol 23 (8) ◽  
pp. 997-1003 ◽  
Author(s):  
Jason K Karimy ◽  
Jinwei Zhang ◽  
David B Kurland ◽  
Brianna Carusillo Theriault ◽  
Daniel Duran ◽  
...  

2005 ◽  
Vol 289 (6) ◽  
pp. C1448-C1456 ◽  
Author(s):  
Elena V. Bouzinova ◽  
Jeppe Praetorius ◽  
Leila V. Virkki ◽  
Søren Nielsen ◽  
Walter F. Boron ◽  
...  

Several studies suggest the involvement of Na+ and HCO3− transport in the formation of cerebrospinal fluid. Two Na+-dependent HCO3− transporters were recently localized to the epithelial cells of the rat choroid plexus (NBCn1 and NCBE), and the mRNA for a third protein was also detected (NBCe2) (Praetorius J, Nejsum LN, and Nielsen S. Am J Physiol Cell Physiol 286: C601–C610, 2004). Our goal was to immunolocalize the NBCe2 to the choroid plexus by immunohistochemistry and immunogold electronmicroscopy and to functionally characterize the bicarbonate transport in the isolated rat choroid plexus by measurements of intracellular pH (pHi) using a dual-excitation wavelength pH-sensitive dye (BCECF). Both antisera derived from COOH-terminal and NH2-terminal NBCe2 peptides localized NBCe2 to the brush-border membrane domain of choroid plexus epithelial cells. Steady-state pHi in choroidal cells increased from 7.03 ± 0.02 to 7.38 ± 0.02 ( n = 41) after addition of CO2/HCO3− into the bath solution. This increase was Na+ dependent and inhibited by the Cl− and HCO3− transport inhibitor DIDS (200 μM). This suggests the presence of Na+-dependent, partially DIDS-sensitive HCO3− uptake. The pHi recovery after acid loading revealed an initial Na+ and HCO3−-dependent net base flux of 0.828 ± 0.116 mM/s ( n = 8). The initial flux in the presence of CO2/HCO3− was unaffected by DIDS. Our data support the existence of both DIDS-sensitive and -insensitive Na+- and HCO3−-dependent base loader uptake into the rat choroid plexus epithelial cells. This is consistent with the localization of the three base transporters NBCn1, Na+-driven Cl− bicarbonate exchanger, and NBCe2 in this tissue.


2017 ◽  
Vol 12 (1) ◽  
pp. 84 ◽  
Author(s):  
Yousef Sadeghi ◽  
Elham Hashemi ◽  
Abbas Aliaghaei ◽  
Afsoun Seddighi ◽  
Abbas Piryaei ◽  
...  

1985 ◽  
Vol 249 (4) ◽  
pp. F470-F477 ◽  
Author(s):  
Q. R. Smith ◽  
C. E. Johanson

The nature of Cl transport and its relation to Na and K transport were analyzed in adult rat lateral ventricle choroid plexus incubated in cerebrospinal fluid (CSF) medium at 37 degrees C and PCO2 = 30 mmHg. In synthetic CSF (extracellular Cl [( Cl]o) = 130 mM), the intracellular Cl [( Cl]i) was three times that estimated for passive distribution. Choroid plexus [Cl]i was not determined by Donnan distribution because [Cl]i remained constant at approximately 50 mM while the [K]i/[K]o ratio was varied 10-fold by drugs and cation substitutions. A [Cl]i/[Cl]o ratio of approximately 0.38 was found when [Cl]o was varied from 15 to 130 mM by isosmotic replacement of Cl with methyl sulfate or isethionate. However, the [Cl]i/[Cl]o ratio increased to greater than 1.0 when [Cl]o was lowered below 5 mM. Reduction in bath temperature to 15 degrees C (CSF PCO2 = 50 mmHg) increased both [Cl]i/[Cl]o and [HCO3]i/[HCO3]o to approximately 0.6. SITS, an inhibitor of Cl-HCO3 transport, reduced [Cl]i by 18 mM, decreasing the [Cl]i/[Cl]o ratio close to the equilibrium value. In contrast, neither furosemide (10(-3) M) nor low CSF [Na]o (3 mM) reduced Cl accumulation. It is concluded that uphill movement of Cl into choroid plexus epithelium occurs primarily by Cl-HCO3 antiport and not by Na-Cl symport.


Physiology ◽  
2010 ◽  
Vol 25 (4) ◽  
pp. 239-249 ◽  
Author(s):  
Helle H. Damkier ◽  
Peter D. Brown ◽  
Jeppe Praetorius

A stable intraventricular milieu is crucial for maintaining normal neuronal function. The choroid plexus epithelium produces the cerebrospinal fluid and in doing so influences the chemical composition of the interstitial fluid of the brain. Here, we review the molecular pathways involved in transport of the electrolytes Na+, K+, Cl−, and HCO3− across the choroid plexus epithelium.


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