The most widely studied stimuli for ion channel activation are changes in membrane voltage and binding of a chemical ligand in a pocket of the channel protein. While modulation by redox potential has also been appreciated our study shows previously unrecognised channel activation via electron donation from the extracellular redox protein thioredoxin (TRX).(1) The ion channel type involved is a member of the Transient Receptor Potential (TRP) family. Activation by TRX led us to consider the relevance of TRP channels to the inflammatory condition of rheumatoid arthritis, where functions of ion channels are relatively unknown and TRX concentrations are high. TRP channel activation was found to be inhibitory for secretion of matrix metalloproteinases, suggesting activation by TRX may have a protective role against disease. Here we expand on our original article and discuss the potential wider implications of the findings in terms of concepts for channel activation and relevance to other ion channel types and systems.