ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Carbonic anhydrases CA4 and CA14 both enhance AE3-mediated Cl--HCO3- exchange in hippocampal neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.International journal of geriatric psychiatry · 2016Trial
- Acetazolamide inhibition of carbonic anhydrase 4 reverses opioid-induced synaptic rearrangements in nucleus accumbens and reduces drug-seeking behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Potential Biological Processes Related to Brain SLC13A5 Across the Lifespan: Weighted Gene Co-Expression Network Analysis from Large Human Transcriptomic Data.Brain sciences · 2026Article
- Kaempferide Promotes Neuroprotection and Functional Recovery After Spinal Cord Injury and is Associated with Differential Regulation of ARG1, CA4, CYP1B1, and OAT.Neuropsychiatric disease and treatment · 2026Article
- Identification of MTURN as a trained immunity-related biomarker for heart failureFrontiers in immunology · 2026Article
- Proteomic Signatures Underlying Sleep, Circadian Activity Patterns, and Major Chronic Diseases.Journal of pineal research · 2025Article
- Carbonic anhydrase 4 disruption and pharmacological inhibition reduce synaptic and behavioral adaptations following oxycodone withdrawal.bioRxiv : the preprint server for biology · 2025Article
- Carbonic anhydrase, its inhibitors and vascular function.Frontiers in molecular biosciences · 2024Review
- Effects of extracellular metabolic acidosis and out-of-equilibrium COFrontiers in physiology · 2024Article
- New isoxazolidinyl-basedJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Upregulation of carbonic anhydrase 1 beneficial for depressive disorder.Acta neuropathologica communications · 2023Article
- Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal.Science advances · 2022Article
- The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.The Journal of physiology · 2022Article
- Amino Acid Nanofibers Improve Glycemia and Confer Cognitive Therapeutic Efficacy to Bound Insulin.Pharmaceutics · 2021Article
- Carbonic anhydrase activation profile of indole-based derivatives.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Activation of carbonic anhydrases from human brain by amino alcohol oxime ethers: towards human carbonic anhydrase VII selective activators.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Review
- The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and pH Homeostasis in Non-Secretory Organs.International journal of molecular sciences · 2020Review
- Carbonic anhydrase IX and acid transport in cancer.British journal of cancer · 2020Review
- NaHCOHypertension (Dallas, Tex. : 1979) · 2019Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Carbonic anhydrase (CA) activity in the brain extracellular space is attributable mainly to isoforms CA4 and CA14. In brain, these enzymes have been studied mostly in the context of buffering activity-dependent extracellular pH transients. Yet evidence from others has suggested that CA4 acts in a complex with anion exchangers (AEs) to facilitate Cl(-)-HCO(3)(-) exchange in cotransfected cells. To investigate whether CA4 or CA14 plays such a role in hippocampal neurons, we studied NH(4)(+)-induced alkalinization of the cytosol, which is mitigated by Cl(-) entry and HCO(3)(-) exit. The NH(4)(+)-induced alkalinization was enhanced when the extracellular CAs were inhibited by the poorly permeant CA blocker, benzolamide, or by inhibitory antibodies specific for either CA4 or CA14. The NH(4)(+)-induced alkalinization was also increased with inhibition of anion exchange by 4,4*-diisothiocyanostilbene-2,2*-disulfonic acid, or by eliminating Cl(-) from the medium. No effect of benzolamide was seen under these conditions, in which no Cl(-)-HCO(3)(-) exchange was possible. Quantitative PCR on RNA from the neuronal cultures indicated that AE3 was the predominant AE isoform. Single-cell PCR also showed that Slc4a3 (AE3) transcripts were abundant in isolated neurons. In hippocampal neurons dissociated from AE3-null mice, the NH(4)(+)-induced alkalinization was much larger than that seen in neurons from wild-type mice, suggesting little or no Cl(-)-HCO(3)(-) exchange in the absence of AE3. Benzolamide had no effect on the NH(4)(+)-induced alkalinization in the AE3 knock-out neurons. Our results indicate that CA4 and CA14 both play important roles in the regulation of intracellular pH in hippocampal neurons, by facilitating AE3-mediated Cl(-)-HCO(3)(-) exchange.
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