Biological Activity
ACCN2 is the cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. ACCN2 is also permeable for Ca2+, Li+ and K+. ACCN2 generates a biphasic current with a fast inactivating and a slow sustained phase. ACCN2 mediates glutamate-independent Ca2+ entry into neurons upon acidosis. This Ca2+ overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. ACCN2 functions as a postsynaptic proton receptor th at influences intracellular Ca2+ concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. It modulates activity in the circuits underlying innate fear.This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels th at contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene is expressed in most if not all brain neurons, and it may be an ion channel subunit; however, its function as an ion channel remains unknown. Alternative splicing of this gene generates 2 transcript products.
