Dual role of acid-sensing ion channels 3 in rheumatoid arthritis: destruction or protection?

Acid-sensing ion channels (ASIC) are voltage-independent cationic channels that open in response to decrease in extracellular pH. Amongst different subtypes, ASIC3 has received much attention in joint inflammatory conditions including rheumatoid arthritis. There have been a number of studies showing that there is an increase in expression of ASIC3 on nerve afferents supplying joints in response to inflammatory stimulus. Accordingly, a number of selective as well as nonselective ASIC3 inhibitors have shown potential in attenuating pain and inflammation in animal models of rheumatoid arthritis. On the other hand, there have been studies showing that ASIC3 may exert protective effects in joint inflammation. ASIC-/- animals, without ASIC3 genes, exhibit more joint inflammation and destruction in comparison to ASIC+/+ animals. The present review discusses the dual nature of ASIC3 in joint inflammation with possible mechanisms.