Characterization of neuropeptide binding to a membrane receptor involved in pain and stroke

Acid-sensing ion channels (ASICs) contribute to neuronal communication. In chronic pain and ischemic stroke, however, tissue acidification and increased release of a neuropeptide called dynorphin activate ASICs to an extent that is toxic to neurons. Targeting the dynorphin-ASIC interaction has therefore therapeutic potential, yet we lack methods to directly assess the interaction. We aim to fluorescently label ASIC and dynorphin to establish FRET-based electrophysiology studies to characterize the mechanism, affinity and kinetics of binding. We anticipate the outcome to aid future design of ASIC inhibitors that could treat chronic pain and ischemia. Further, it will have an impact beyond this project, as it enables binding studies in intact membranes and with high temporal resolution.