Redox regulation of ion channels

Reactive oxygen species and reactive nitrogen species (ROS/RNS) are often by-products of biochemical reactions, but are increasingly recognized as important second messengers involved in regulation of distinct cellular functions. Mild and reversible oxidation of certain amino acids within protein polypeptide chains is known to precisely control the function of transcription factors, protein kinases and phosphatases, receptors, pumps, ion channels, and so on. Conversely, under pathological conditions, high amounts of oxidants irreversibly oxidize DNA, lipids, and proteins and have deleterious effects on cells, ultimately causing cell death. ROS/RNS can thus be involved in the initiation and progression of many pathological conditions. Within this Forum, seven reviews and one original article summarize the current knowledge regarding redox regulation of various ion channels and ion conducting receptors. These include the recently identified mitochondrial Ca2+ uniporter and Orai Ca2+ channels, as well as selected members of the families of transient receptor potential, voltage-gated Ca2+, P2X, voltage-gated K+, and IP3R/RyR channels. In summary, all authors agree on the functional importance of redox-ion channel interplay. However, it is also clear that this is an emerging field of research where much has to be learned about intra- and extracellular sources, concentrations, and types of oxidants. Given their often short-lived nature and effective cellular buffering systems, the development of tools to measure local ROS production in living cells as well as detailed proteomic approaches to pinpoint protein targets and redox modifications are of importance.