Acid-Sensing Ion Channels

Acid-sensing ion channels (ASIC) are members of the ENaC/Deg (epithelial amiloride-sensitive Na⁺ channel and degenerin) family of ion channels and are widely expressed in neurons of the central and peripheral nervous system. They are voltage-insensitive, Na⁺ permeable channels that are activated by low extracellular pH.

ASIC subunits contain two putative transmembrane domains and assemble as homotrimers or heterotrimers. To date, five genes of the ASIC family have been identified. ASICs 1-3 are expressed in nociceptive sensory neurons and are involved in regulating mechanoceptor and nociceptor function. They are upregulated in the dorsal root ganglion (DRG) and spinal cord in response to inflammation, and have a role in visceral and cutaneous mechanosensation. ASICs 1 and 2 are additionally expressed in the central nervous system and, because they are sensitive to acid, are implicated in conditions associated with ischemia and local acidosis, such as stroke and multiple sclerosis. ASIC1a, 1b and 2a, 2b are splice variants of ASIC1 and ASIC2, respectively. ASIC4 is expressed in many brain regions, as well as in the spinal cord and cerebellum, and may be involved in modulating fear and anxiety, while ASIC5 is an orphan member of the family, which is abundantly expressed in the cerebellum and to a lesser extent in the brain, liver and intestine.

External sources of pharmacological information for Acid-Sensing Ion Channels :

• IUPHAR Receptor Code

Acid-Sensing Ion Channel Gene Data