Zinc-activated ion channel (ZACN)

The Zinc-activated ion channel (ZACN) is a member of the Cys-loop family of ligand-gated ion channels, which also includes nicotinic acetylcholine and serotonin 5-HT3 receptors (UniProt Q401N2). Unlike most family members that respond to organic neurotransmitters, ZACN is specifically activated by extracellular zinc ions (Davies et al., 2003). It typically forms homopentameric structures that function as non-selective cation channels, allowing the influx of sodium and calcium ions to mediate cellular depolarization (Madjroh et al., 2021). ZACN expression is notably high in the human hippocampus, striatum, and pancreas, suggesting roles in synaptic plasticity and endocrine regulation (Houtani et al., 2005). Although it is considered a potential therapeutic target for neurodegenerative and metabolic diseases, its clinical utility is currently limited by the absence of potent, selective small-molecule ligands (Trattnig et al., 2016). Research indicates that ZACN may also be modulated by protons and certain quaternary ammonium compounds, providing a basis for future drug discovery efforts (Steinat et al., 2019).

Other names

ZACLGICZ1Ligand-gated ion-channel zinc-activated 1L2

Zinc-activated ion channel agonists bind to the extracellular domain of the homopentameric receptor, inducing a conformational change that opens a transmembrane pore permeable to sodium, potassium, and calcium ions, resulting in membrane depolarization.