Acid-sensing ion channel 3 (ASIC3)

Acid-sensing ion channel 3 (ASIC3) is a member of the epithelial sodium channel/degenerin (ENaC/DEG) ion channel family that responds to changes in extracellular pH by allowing sodium influx into cells[2][3]. ASIC3 is highly expressed in peripheral sensory neurons, especially those involved in pain pathways (nociceptors), and is distinguished by its ability to encode both transient and sustained currents in response to acidic environments, allowing it to signal both acute and prolonged tissue acidosis[2][4]. ASIC3 is implicated in multiple physiological and pathological processes, including the detection of noxious stimuli, mediation of inflammatory pain, and potential roles in tumor progression and neuroinflammation[2][6][7]. Its unique pharmacology and tissue distribution make it an attractive target for the development of novel analgesics, as well as a potential biomarker or therapeutic target in diseases such as cancer and neurodegenerative disorders[2][7]. Interactions with endogenous (e.g., ATP, serotonin, NO) and exogenous modulators (e.g., amiloride, guanidinium derivatives) continue to be explored for therapeutic exploitation[3][6][7].

Other names

Acid sensing ion channel 3ASIC-3ACCN3DRASICIon channelAcid sensor

Inhibition by amiloride blocks cation influx and reduces ASIC3-mediated currents; non-proton ligands (e.g., GMQ, Agmatine) directly activate or modulate the channel, producing sustained depolarization; many candidate analgesics target proton-induced activation or modulation of channel gating