Anion exchange protein 3 (AE3)

Anion exchange protein 3 (AE3) is a member of the solute carrier family 4, encoded by the SLC4A3 gene, and functions as a sodium-independent, electroneutral anion exchanger that mediates bidirectional exchange of chloride (Cl^−) and bicarbonate (HCO₃^−) across the plasma membrane. AE3 is highly expressed in excitable tissues, predominantly brain neurons, heart (cardiac muscle), and retina, where it regulates intracellular pH and bicarbonate homeostasis, thus playing key roles in modulating neuronal excitability and cardiac electrophysiology. Two main isoforms are known: a brain/neuron-predominant form and a cardiac-specific form, generated by alternative splicing. Genetic mutations or disruption of SLC4A3 are causally linked to short QT syndrome type 7—a rare, potentially fatal cardiac arrhythmia—as well as certain forms of epilepsy and retinal degeneration. AE3 activity is uniquely sensitive to inhibition by DIDS, distinguishing it functionally from family members AE1 and AE2. As a disease-associated transporter, AE3 is of research interest for its roles in pathophysiology and potential as a therapeutic target.

Other names

SLC4A3AE3Anion exchange protein 3Anion exchanger 3SLC2CCAE3/BAE3Cardiac/brain band 3-like proteinNeuronal band 3-like proteinSQT7 (refers to disease association, Short QT syndrome 7)Solute carrier family 4 member 3

Inhibition of chloride-bicarbonate exchange leading to altered pH homeostasis by DIDS and similar anion exchange inhibitors