Figure 2.

Acid sensing ion channels (ASIC) are gated by increasing concentrations of H${}^{+}$. Two G-protein pathways modulate the function of ASICs. Activation of G$\alpha$${}_{q/11}$-coupled receptors (left) leads to activation of phospholipase C (PLC) which hydrolyzes phosphatitylinositol 1,4, bisphosphate (PIP${}_2$) into inositiol 1,4,5 trisphosphate (IP${}_3$) and diacylglycerol (DAG). DAG activates protein kinase C (PKC) which phosphorylates ASICs increasing their function. The interaction of PKC with ASICs requires the presence of PICK-1 (protein interacting with C-kinase 1). By contrast, activation of G$\alpha$${}_{q/11}$-coupled V${}_{1A}$ receptors (center) were shown to decrease ASIC-mediated currents via an unknown mechanism. Stimulation of G$\alpha$${}_{i/o}$-coupled receptors (right) was shown to decrease currents through ASICs involving an undetermined mechanism.