| First Author | Hentschke M | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 1 | Pages | 182-91 |
| PubMed ID | 16354689 | Mgi Jnum | J:104157 |
| Mgi Id | MGI:3611402 | Doi | 10.1128/MCB.26.1.182-191.2006 |
| Citation | Hentschke M, et al. (2006) Mice with a Targeted Disruption of the Cl-/HCO3- Exchanger AE3 Display a Reduced Seizure Threshold. Mol Cell Biol 26(1):182-91 |
| abstractText | Neuronal activity results in significant pH shifts in neurons, glia, and interstitial space. Several transport mechanisms are involved in the fine-tuning and regulation of extra- and intracellular pH. The sodium-independent electroneutral anion exchangers (AEs) exchange intracellular bicarbonate for extracellular chloride and thereby lower the intracellular pH. Recently, a significant association was found with the variant Ala867Asp of the anion exchanger AE3, which is predominantly expressed in brain and heart, in a large cohort of patients with idiopathic generalized epilepsy. To analyze a possible involvement of AE3 dysfunction in the pathogenesis of seizures, we generated an AE3-knockout mouse model by targeted disruption of Slc4a3. AE3-knockout mice were apparently healthy, and neither displayed gross histological and behavioral abnormalities nor spontaneous seizures or spike wave complexes in electrocorticograms. However, the seizure threshold of AE3-knockout mice exposed to bicuculline, pentylenetetrazole, or pilocarpine was reduced, and seizure-induced mortality was significantly increased compared to wild-type littermates. In the pyramidal cell layer of the hippocampal CA3 region, where AE3 is strongly expressed, disruption of AE3 abolished sodium-independent chloride-bicarbonate exchange. These findings strongly support the hypothesis that AE3 modulates seizure susceptibility and, therefore, are of significance for understanding the role of intracellular pH in epilepsy. |
