Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability.
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.
Jacobs
Stefan
S
Department of Human Genetics and Zentrum für Molekulare Neurobiologie Hamburg, University of Hamburg, D-20249 Hamburg, Germany.
Ruusuvuori
Eva
E
Sipilä
Sampsa T
ST
Haapanen
Aleksi
A
Damkier
Helle H
HH
Kurth
Ingo
I
Hentschke
Moritz
M
Schweizer
Michaela
M
Rudhard
York
Y
Laatikainen
Linda M
LM
Tyynelä
Jaana
J
Praetorius
Jeppe
J
Voipio
Juha
J
Hübner
Christian A
CA
D000818:Animals; D001522:Behavior, Animal; D001692:Biological Transport; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007858:Learning; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000502:physiology*
D027963:Chloride-Bicarbonate Antiporters; D007477:Ions; C526208:Slc4a10 protein, mouse; D027982:Sodium-Bicarbonate Symporters