Figure 1.

Modulation of ASICs by extracellular and intracellular signaling molecules. ASICs are activated by protons and non-proton molecules such as GMQ (for ASIC3 only). Activation of ASIC1a, voltage-gated calcium channels (VGCCs), glutamate receptors (GluRs) and the releases of intracellular Ca²⁺ pools increases intracellular [Ca²⁺]ⁱ. The resulting increase in [Ca²⁺]ⁱ triggers downstream signaling events, including CaMKII activation. ASIC activity is also regulated by interactions with CaMKII, PKA, PKC, AKAP150, calcineurin, PICK1 and possibly other PDZ-domain proteins such as CIPP.