Acid-sensing ion channel subunit 3 (ASIC3)

Acid-sensing ion channel subunit 3 (ASIC3) is a proton-gated, amiloride-sensitive sodium channel primarily expressed in peripheral sensory neurons, where it detects extracellular acidification and plays a major role in acid-induced pain (nociception), mechanosensation, and heat pain[2][3]. ASIC3 belongs to the DEG/ENaC ion channel superfamily and assembles as a trimer (homomeric or heteromeric, often with ASIC2a), mediating fast, excitatory sodium currents upon acute drops in extracellular pH[1][3][4]. ASIC3 has higher proton sensitivity and faster gating kinetics compared to other ASIC family members and is implicated in pain from inflammation, ischemia, and tissue damage, as well as in broader roles in neuronal excitability and some pathological conditions[3][5]. The channel is modulated by drugs such as amiloride (inhibitor) and GMQ (non-proton ligand and modulator), but its widespread neuronal distribution presents challenges for therapeutic targeting[4][2].

Other names

Acid-sensing ion channel 3ACCN3DRASICSLNAC1TNAC1hASIC3hTNaC1TNaC1Amiloride-sensitive cation channel 3Neuronal amiloride-sensitive cation channel 3Testis sodium channel 1modulatory subunit of ASIC2aproton-gated cation channel subunit

Blockade of proton-gated ion flow (e.g. by amiloride) Modulation of channel activation/gating (e.g. GMQ binding alters activation state)