Disruption of Slc4a10 augments neuronal excitability and modulates synaptic short-term plasticity
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Slc4a10 is a Na(+)-coupled Cl(-)-HCO3 (-) exchanger, which is expressed in principal and inhibitory neurons as well as in choroid plexus epithelial cells of the brain. Slc4a10 knockout (KO) mice have collapsed brain ventricles and display an increased seizure threshold, while heterozygous deletions in man have been associated with idiopathic epilepsy and other neurological symptoms. To further characterize the role of Slc4a10 for network excitability, we compared input-output relations as well as short and long term changes of evoked field potentials in Slc4a10 KO and wildtype (WT) mice. While responses of CA1 pyramidal neurons to stimulation of Schaffer collaterals were increased in Slc4a10 KO mice, evoked field potentials did not differ between genotypes in the stratum radiatum or the neocortical areas analyzed. Paired pulse facilitation was diminished in the hippocampus upon disruption of Slc4a10. In the neocortex paired pulse depression was increased. Though short term plasticity is modulated via Slc4a10, long term potentiation appears independent of Slc4a10. Our data support that Slc4a10 dampens neuronal excitability and thus sheds light on the pathophysiology of SLC4A10 associated pathologies.
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Slc4a10 loops downstream to a schizophrenia-associated single-nucleotide variant that overlaps a region of activity-decommissioned H3K27ac.
“One such gene is Slc4a10 (ref. 45), which loops downstream to a schizophrenia-associated SNV (Extended Data Fig. 10f) that overlaps a region of activity-decommissioned H3K27ac”
From Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression (2020) · cites this paper as [45]
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- Authors
- Sinning, A., Liebmann, L., & Hübner, C. A.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Jena University Hospital (DE)
- ORCID
- Sinning, Anne
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2015-06-16
- Volume
- 9
- Pages
- 223-223
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC4468864
- OpenAlex
- W1547480653
- Cited by
- 32
- References
- 50
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 1 · 2015: 1
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (01GQ0923, HU 800/8-1)
- Bundesministerium für Bildung und Forschung (01GQ0923)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- SLC4A10, neuronal excitability, paired-pulse facilitation, paired-pulse depression, long-term potentiation, CA1 pyramidal neurons, Schaffer collaterals, evoked field potentials, idiopathic epilepsy, hippocampus, neocortex, choroid plexus epithelial cells
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