Redox Regulation of K⁺ Channel: Role of Thioredoxin

Significance: Potassium channels regulate the influx and efflux of K⁺ ions in various cell types that generate and propagate action potential associated with excitation, contraction, and relaxation of various cell types. Although redox active cysteines are critically important for channel activity, the redox regulation of K⁺ channels by thioredoxin (Trx) has not been systematically reviewed. Recent Advances: Redox regulation of K⁺ channel is now increasingly recognized as drug targets in the pathological condition of several cardiovascular disease processes. The role of Trx in regulation of these channels and its implication in pathological conditions have not been adequately reviewed. This review specifically focuses on the redox-regulatory role of Trx on K⁺ channel structure and function in physiological and pathophysiological conditions. Critical Issues: Ion channels, including K⁺ channel, have been implicated in the functioning of cardiomyocyte excitation-contraction coupling, vascular hyperpolarization, cellular proliferation, and neuronal stimulation in physiological and pathophysiological conditions. Although oxidation-reduction of ion channels is critically important in their function, the role of Trx, redox regulatory protein in regulation of these channels, and its implication in pathological conditions need to be studied to gain further insight into channel function. Future Directions: Future studies need to map all redox regulatory pathways in channel structure and function using novel mouse models and redox proteomic and signal transduction studies, which modulate various currents and altered excitability of relevant cells implicated in a pathological condition. We are yet at infancy of studies related to redox control of various K⁺ channels and structured and focused studies with novel animal models. Antioxid. Redox Signal. 41, 818-844.