ArticleMolecular and cellular biology2006
Mice with a targeted disruption of the Cl-/HCO3- exchanger AE3 display a reduced seizure threshold.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 114 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Transport mechanism of the SLC4 proteins-Lessons from recent structural and computational studies.The Journal of biological chemistry · 2026Review
- Acid-Base homeostasis in the brain: regional heterogeneity and different Acid-Base transporters.Pflugers Archiv : European journal of physiology · 2026Review
- The structural insight into the functional modulation of human anion exchanger 3.Nature communications · 2024Article
- Transient Receptor Potential Channels in the Healthy and Diseased Blood-Brain Barrier.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Review
- Effects of extracellular metabolic acidosis on the homeostasis of intracellular pH in hippocampal neurons.Frontiers in physiology · 2024Article
- Effects of extracellular metabolic acidosis and out-of-equilibrium COFrontiers in physiology · 2024Article
- Potential Theranostic Roles of SLC4 Molecules in Human Diseases.International journal of molecular sciences · 2023Review
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
- Levetiracetam Mechanisms of Action: From Molecules to Systems.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Chloride Homeostasis in Developing Motoneurons.Advances in neurobiology · 2022Article
- Simultaneous Monitoring of pH and Chloride (ClInternational journal of molecular sciences · 2021Article
- Neuronal Swelling: A Non-osmotic Consequence of Spreading Depolarization.Neurocritical care · 2021Article
- Rapid volume pulsation of the extracellular space coincides with epileptiform activity in mice and depends on the NBCe1 transporter.The Journal of physiology · 2021Article
- The Role of TRP Channels and PMCA in Brain Disorders: Intracellular Calcium and pH Homeostasis.Frontiers in cell and developmental biology · 2021Review
- Glial Chloride Homeostasis Under Transient Ischemic Stress.Frontiers in cellular neuroscience · 2021Article
- NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data.Cells · 2020Review
- Fatty Acid Amides Synthesized from Andiroba Oil (Pharmaceuticals (Basel, Switzerland) · 2020Article
- Deletion of the Na/HCOScientific reports · 2019Article
- Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and IdentifiesJournal of clinical medicine · 2019Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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