Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability
- PMID: 18165320
- PMCID: PMC2224208
- DOI: 10.1073/pnas.0705487105
Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability
Abstract
Members of the SLC4 bicarbonate transporter family are involved in solute transport and pH homeostasis. Here we report that disrupting the Slc4a10 gene, which encodes the Na(+)-coupled Cl(-)-HCO(3)(-) exchanger Slc4a10 (NCBE), drastically reduces brain ventricle volume and protects against fatal epileptic seizures in mice. In choroid plexus epithelial cells, Slc4a10 localizes to the basolateral membrane. These cells displayed a diminished recovery from an acid load in KO mice. Slc4a10 also was expressed in neurons. Within the hippocampus, the Slc4a10 protein was abundant in CA3 pyramidal cells. In the CA3 area, propionate-induced intracellular acidification and attenuation of 4-aminopyridine-induced network activity were prolonged in KO mice. Our data indicate that Slc4a10 is involved in the control of neuronal pH and excitability and may contribute to the secretion of cerebrospinal fluid. Hence, Slc4a10 is a promising pharmacological target for the therapy of epilepsy or elevated intracranial pressure.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Similar articles
-
Genetic ablation of Slc4a10 alters the expression pattern of transporters involved in solute movement in the mouse choroid plexus.Am J Physiol Cell Physiol. 2012 May 15;302(10):C1452-9. doi: 10.1152/ajpcell.00285.2011. Epub 2012 Feb 22. Am J Physiol Cell Physiol. 2012. PMID: 22357733
-
Na+-dependent HCO3- import by the slc4a10 gene product involves Cl- export.J Biol Chem. 2010 Aug 27;285(35):26998-7007. doi: 10.1074/jbc.M110.108712. Epub 2010 Jun 21. J Biol Chem. 2010. PMID: 20566632 Free PMC article.
-
Lack of the sodium-driven chloride bicarbonate exchanger NCBE impairs visual function in the mouse retina.PLoS One. 2012;7(10):e46155. doi: 10.1371/journal.pone.0046155. Epub 2012 Oct 9. PLoS One. 2012. PMID: 23056253 Free PMC article.
-
Na(+) dependent acid-base transporters in the choroid plexus; insights from slc4 and slc9 gene deletion studies.Front Physiol. 2013 Oct 22;4:304. doi: 10.3389/fphys.2013.00304. Front Physiol. 2013. PMID: 24155723 Free PMC article. Review.
-
Cation-coupled bicarbonate transporters.Compr Physiol. 2014 Oct;4(4):1605-37. doi: 10.1002/cphy.c130005. Compr Physiol. 2014. PMID: 25428855 Free PMC article. Review.
Cited by 66 articles
-
Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1.Sci Rep. 2020 Jul 3;10(1):11017. doi: 10.1038/s41598-020-67291-0. Sci Rep. 2020. PMID: 32620847 Free PMC article.
-
TimeMeter assesses temporal gene expression similarity and identifies differentially progressing genes.Nucleic Acids Res. 2020 May 21;48(9):e51. doi: 10.1093/nar/gkaa142. Nucleic Acids Res. 2020. PMID: 32123905 Free PMC article.
-
Genetic disruption of slc4a10 alters the capacity for cellular metabolism and vectorial ion transport in the choroid plexus epithelium.Fluids Barriers CNS. 2020 Jan 7;17(1):2. doi: 10.1186/s12987-019-0162-5. Fluids Barriers CNS. 2020. PMID: 31906971 Free PMC article.
-
Expression, Localization, and Effect of High Salt Intake on Electroneutral Na+/HCO3 - Cotransporter NBCn2 in Rat Small Intestine: Implication in Intestinal NaCl Absorption.Front Physiol. 2019 Oct 29;10:1334. doi: 10.3389/fphys.2019.01334. eCollection 2019. Front Physiol. 2019. PMID: 31736772 Free PMC article.
-
Deletion of the Na/HCO3 Transporter NBCn1 Protects Hippocampal Neurons from NMDA-induced Seizures and Neurotoxicity in Mice.Sci Rep. 2019 Nov 5;9(1):15981. doi: 10.1038/s41598-019-52413-0. Sci Rep. 2019. PMID: 31690738 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources
-
Molecular Biology Databases
-
Miscellaneous