Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability

被引:130
作者
Jacobs, Stefan [1 ]
Ruusuvuori, Eva [2 ]
Sipila, Sampsa T. [2 ,3 ]
Haapanen, Aleksi [4 ]
Damkier, Helle H. [5 ]
Kurth, Ingo [1 ]
Hentschke, Moritz [1 ]
Schweizer, Michaela
Rudhard, York
Laatikainen, Linda M. [2 ]
Tyynela, Jaana
Praetorius, Jeppe [5 ]
Voipio, Juha [2 ]
Huebner, Christian A. [1 ,6 ]
机构
[1] Univ Hamburg, Dept Human Genet, D-20249 Hamburg, Germany
[2] Univ Helsinki, Dept Biol Environm Sci, Helsinki 00014, Finland
[3] Univ Helsinki, Ctr Hosp, Dept Clin Neurophysiol, FIN-00290 Helsinki, Finland
[4] Univ Helsinki, Cent Hosp, Inst Biomed Biochem Biomed, Dept Neurol,Expt MRI Lab, FIN-00290 Helsinki, Finland
[5] Aarhus Univ, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark
[6] Univ Jena, Dept Clin Chem, D-07747 Jena, Germany
关键词
cerebrospinal fluid; epilepsy; ion transport; knockout mouse; pH regulation;
D O I
10.1073/pnas.0705487105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Members of the SLC4 bicarbonate transporter family are involved in solute transport and pH homeostasis. Here we report that disrupting the S1c4a10 gene, which encodes the Na+-coupled Cl--HCO3- 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. 5lc4a10 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.
引用
收藏
页码:311 / 316
页数:6
相关论文
共 40 条
[1]   Genetic diseases of acid-base transporters [J].
Alper, SL .
ANNUAL REVIEW OF PHYSIOLOGY, 2002, 64 :899-923
[2]   CONCENTRATION OF CARBON-DIOXIDE, INTERSTITIAL PH AND SYNAPTIC TRANSMISSION IN HIPPOCAMPAL-FORMATION OF THE RAT [J].
BALESTRINO, M ;
SOMJEN, GG .
JOURNAL OF PHYSIOLOGY-LONDON, 1988, 396 :247-266
[3]   Mri-based quantification of cerebral edema in individual SHRSP rats using averaged criteria determined before the occurrence of edema [J].
Blezer, ELA ;
Nicolay, K ;
Viergever, MA ;
Koomans, HA ;
Joles, JA .
MAGNETIC RESONANCE IMAGING, 1999, 17 (06) :903-907
[4]   Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold [J].
Boettger, T ;
Rust, MB ;
Maier, H ;
Seidenbecher, T ;
Schweizer, M ;
Keating, DJ ;
Faulhaber, J ;
Ehmke, H ;
Pfeffer, C ;
Scheel, O ;
Lemcke, B ;
Horst, J ;
Leuwer, R ;
Pape, HC ;
Völkl, H ;
Hübner, CA ;
Jentsch, TJ .
EMBO JOURNAL, 2003, 22 (20) :5422-5434
[5]   Na+-dependent HCO3- uptake into the rat choroid plexus epithelium is partially DIDS sensitive [J].
Bouzinova, EV ;
Praetorius, J ;
Virkki, LV ;
Nielsen, S ;
Boron, WF ;
Aalkjaer, C .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2005, 289 (06) :C1448-C1456
[6]  
Buzaki G., 2006, Rhythms of the Brain
[7]   HIPPOCAMPAL SHARP WAVES - THEIR ORIGIN AND SIGNIFICANCE [J].
BUZSAKI, G .
BRAIN RESEARCH, 1986, 398 (02) :242-252
[8]   THE EFFECT OF ACETAZOLEAMIDE ON THE CHEMICAL COMPOSITION OF THE AQUEOUS HUMOUR AND CEREBROSPINAL FLUID OF SOME MAMMALIAN SPECIES AND ON THE RATE OF TURNOVER OF NA-24 IN THESE FLUIDS [J].
DAVSON, H ;
LUCK, CP .
JOURNAL OF PHYSIOLOGY-LONDON, 1957, 137 (02) :279-293
[9]   EFFECTS OF SOME INHIBITORS AND ACCELERATORS OF SODIUM TRANSPORT ON TURNOVER OF NA-22 IN CEREBROSPINAL FLUID AND BRAIN [J].
DAVSON, H ;
SEGAL, MB .
JOURNAL OF PHYSIOLOGY-LONDON, 1970, 209 (01) :131-&
[10]   STILBENES INHIBIT EXCHANGE OF CHLORIDE BETWEEN BLOOD, CHOROID-PLEXUS AND CEREBROSPINAL-FLUID [J].
DENG, QS ;
JOHANSON, CE .
BRAIN RESEARCH, 1989, 501 (01) :183-187