ArticleThe Journal of general physiology2016
Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl-/HCO3- exchanger.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Transport mechanism of the SLC4 proteins-Lessons from recent structural and computational studies.The Journal of biological chemistry · 2026Review
- Molecular determinants of [Formula: see text] and cation transport in the human cation-dependent ClAmerican journal of physiology. Cell physiology · 2025Article
- Urinary sodium wasting and disrupted collecting duct function in mice with distal renal tubular acidosis mutations.Disease models & mechanisms · 2025Article
- KInternational journal of molecular sciences · 2024Article
- The role of NaPflugers Archiv : European journal of physiology · 2024Review
- Novel functions of the anion exchanger AE4 (SLC4A9).Pflugers Archiv : European journal of physiology · 2024Review
- Potential Theranostic Roles of SLC4 Molecules in Human Diseases.International journal of molecular sciences · 2023Review
- Signaling Roleplay between Ion Channels during Mammalian Sperm Capacitation.Biomedicines · 2023Review
- The AE4 transporter mediates kidney acid-base sensing.Nature communications · 2023Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes.Physiological reports · 2022Article
- A Review on the Role of Bicarbonate and Proton Transporters during Sperm Capacitation in Mammals.International journal of molecular sciences · 2022Review
- Role of SLC4 and SLC26 solute carriers during oxidative stress.Acta physiologica (Oxford, England) · 2022Review
- Activation of the Ae4 (Slc4a9) cation-driven ClAmerican journal of physiology. Gastrointestinal and liver physiology · 2021Article
- The Bicarbonate Transporter (MoAE4) Localized on Both Cytomembrane and Tonoplast Promotes Pathogenesis inJournal of fungi (Basel, Switzerland) · 2021Article
- "SLC-omics" of the kidney: solute transporters along the nephron.American journal of physiology. Cell physiology · 2021Review
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- Article
- 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
- Genome-wide identification of Chiari malformation type I associated candidate genes and chromosomal variations.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
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5 authors at 3 institutions in 1 country.
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Abstract
Ae4 (Slc4a9) belongs to the Slc4a family of Cl(-)/HCO3 (-) exchangers and Na(+)-HCO3 (-) cotransporters, but its ion transport cycle is poorly understood. In this study, we find that native Ae4 activity in mouse salivary gland acinar cells supports Na(+)-dependent Cl(-)/HCO3 (-) exchange that is comparable with that obtained upon heterologous expression of mouse Ae4 and human AE4 in CHO-K1 cells. Additionally, whole cell recordings and ion concentration measurements demonstrate that Na(+) is transported by Ae4 in the same direction as HCO3 (-) (and opposite to that of Cl(-)) and that ion transport is not associated with changes in membrane potential. We also find that Ae4 can mediate Na(+)-HCO3 (-) cotransport-like activity under Cl(-)-free conditions. However, whole cell recordings show that this apparent Na(+)-HCO3 (-) cotransport activity is in fact electroneutral HCO3 (-)/Na(+)-HCO3 (-) exchange. Although the Ae4 anion exchanger is thought to regulate intracellular Cl(-) concentration in exocrine gland acinar cells, our thermodynamic calculations predict that the intracellular Na(+), Cl(-), and HCO3 (-) concentrations required for Ae4-mediated Cl(-) influx differ markedly from those reported for acinar secretory cells at rest or under sustained stimulation. Given that K(+) ions share many properties with Na(+) ions and reach intracellular concentrations of 140-150 mM (essentially the same as extracellular [Na(+)]), we hypothesize that Ae4 could mediate K(+)-dependent Cl(-)/HCO3 (-) exchange. Indeed, we find that Ae4 mediates Cl(-)/HCO3 (-) exchange activity in the presence of K(+) as well as Cs(+), Li(+), and Rb(+) In summary, our results strongly suggest that Ae4 is an electroneutral Cl(-)/nonselective cation-HCO3 (-) exchanger. We postulate that the physiological role of Ae4 in secretory cells is to promote Cl(-) influx in exchange for K(+)(Na(+)) and HCO3 (-) ions.
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