Conformational dynamics and role of the acidic pocket in ASIC pH-dependent gating

Significance Many physiological processes are regulated by pH. The acid-sensing ion channels (ASICs) are neuronal pH sensors involved in learning, fear behavior, neurodegeneration after ischemic stroke, and pain sensation. The mechanism by which acidic pH activates ASICs is still poorly understood. We show here that the “acidic pocket,” the binding site of several toxins, is not essential for channel function but has, rather, a modulatory role....