ASIC3 is a member of a family of Na+ channels that are activated by external protons. The family includes another three members ASIC1, ASIC2 and ASIC4. The ASICs are in fact part of a larger superfamily termed degenerin/epithelial Na+ channels (DEG/ENaC) and share with it the same basic characteristics: two transmembrane spanning domains, a large extracellular domain and short intracellular N and C termini.
The functional channel is composed of 4 subunits that can be assembled as homo or heterotetramers with the other ASIC subunits.
A drop in external pH opens the channel resulting in an inward cation current that is quickly inactivated even in the continuous presence of protons in the medium, although a small residual current may persist.
Several lines of evidence indicate that ASIC3 may function as a pain sensor. First, it is specifically located in dorsal root ganglia (DRG) neurons and in nociceptors that are involved in pain detection and transmission. In addition, in conditions such as inflammation and cardiac ischemia that include tissue acidosis and thus pain, ASIC3 currents have been detected. Finally, ASIC3 deficient mice display altered sensitivity to high intensity pain produced by heat or acid.
Interestingly, while in rats ASIC3 is expressed almost exclusively in DRG neurons, in humans its expression is more widespread suggesting a more extensive role in human nociception.
