ASIC Activation Mechanisms Delineated through Genetic Code Expansion

Abstract

Acid-sensing Ion Channels (ASICs) are a unique class of ion channels that are activated through acidification of the extracellular space. These trimeric sodium-selective ion channels are found in the central and peripheral nervous system, where they are critical players in a myriad of conditions including ischemic cell death, synaptic plasticity, and fear conditioning. As such, determining how these channels function on a molecular level will aid the development of useful pharmacological tools. Currently, ASIC activation is thought to require protonation of acidic side chains in two distinct domains: the acidic pocket and the palm domain.