Small molecule ion channel match making: a natural fit for new ASIC ligands.

ASICs (acid-sensing ion channels) are proton-gated channels that are important for pain sensation. New work by Yu and coworkers in this issue of Neuron identifies synthetic ligands and related small molecules found in the inflammatory soup that activate ASICs. These new findings highlight the power of small molecule screening to find new compounds that can control channel function. They also demonstrate how the discovery and characterization of such molecules can lead to new insights regarding channel mechanism and natural ligands.