Kenton J. Swartz

Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Extracellular adenosine 5′-triphosphate (ATP) activates P2X receptor channels (P2XRs) that serve important roles in the immune and nervous systems.

eLife Assessment In this valuable study, Huffer et al posit that non-cold sensing members of the TRPM subfamily of ion channels (e.g., TRPM2, TRPM4, TRPM5) contain a binding pocket for icilin that overlaps with the one found in the cold-activated TRPM8 channel. After examining a body of TRP channel cryo-EM structures to identify the conserved site, this study presents convincing electrophysiological evidence supporting the presence of an icilin binding pocket within TRPM4.

Abstract Transient Receptor Potential (TRP) channels are a large and diverse family of tetrameric cation selective channels that are activated by many different types of stimuli, including noxious heat or cold, organic ligands such as vanilloids or cooling agents, or intracellular Ca2+. Structures available for all subtypes of TRP channels reveal that the transmembrane domains are closely related despite their unique sensitivity to activating stimuli.