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.
journal_name
Proc Natl Acad Sci U S Aauthors
Jacobs S,Ruusuvuori E,Sipilä ST,Haapanen A,Damkier HH,Kurth I,Hentschke M,Schweizer M,Rudhard Y,Laatikainen LM,Tyynelä J,Praetorius J,Voipio J,Hübner CAdoi
10.1073/pnas.0705487105subject
Has Abstractpub_date
2008-01-08 00:00:00pages
311-6issue
1eissn
0027-8424issn
1091-6490pii
0705487105journal_volume
105pub_type
杂志文章abstract::Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R1...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1616502114
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