Fig. 2

The structure and function of ASICs. a A trimeric ASIC channel comprises three subunits. Each subunit constructs “a hand holding a ball” structure to sense the extracellular proton and regulate the proton-gated currents. There are three major categories of non-proton regulators (synthetic/nature compound, endogenous metabolites, and divalent cations) to activate or modulate ASICs in a conformational change of structure. b The ASIC1a (or ASIC1b, ASIC2a) homomeric channel mediates a transient current, whereas the ASIC3 homomeric channel mediates a biphasic current containing a transient component followed by a non-inactivated sustained component. c, d The non-proton regulators (e.g., 1 mM GMQ) may shift the activation (open circle) or inactivation (filled circle) curve by changing the conformation of ASIC channels and enhance the window current (the shadow region underneath the dotted lines)