|Recommended name:||Acid-sensing ion channel 3|
|Synonyms:||ACCN3, SLNAC1, TNAC1|
|Sequence length:||531 AA.|
Acid-sensing ion channels (ASICs) belong to the degenerin-epithelial sodium channel (DEG-ENaC) superfamily. The structure consists of two hydrophobic transmembrane domains, a large cysteine-rich extracellular loop, and short intracellular N- and C-termini. Four genes encode at least six different ASIC subunits, namely ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4. The figures show the crystal structures of ASIC1 at high and low pH with a resolution of 2.80 Å and 3.36 Å.
The voltage-independent, amiloride-sensitive channels are involved in various processes, such as nociception, mechanosensation or taste. ASICs are activated by extracellular acidosis and have different pH sensitivities from 3.8 to 6.8 to detect a wide range of pH changes.
The figure shows a selection of different experimentally determined inhibitors that show a great structural variety. There are some divalent and trivalent ions that inhibit the activity of certain ASICSs. Amiloride, which is a diuretic, acts as a pore blocker. Non-steroidal-inflammatory drugs (NSAIDs) also inhibit the function of these channels. Some animal toxins (psalmatoxin and APETx2) have been found to inhibit specific ASICs. Recently, it has been shown that mambalgin, a three-finger peptide from the venom of the black mamba, suppresses pain in mice without toxicity and fewer side effects than morphine. These peptides could be useful in the analgesic treatment of chronic respiratory diseases instead of morphine, because there is no danger of addiction or other side effects, such as constipation. ASICs are promising targets but there is still a lot of research to perform.