Oxidative modification of M-type K+ channels as a mechanism of cytoprotective neuronal silencing

摘要: Voltage-gated K+ channels of the Kv7 family underlie neuronal M current that regulates action potential firing. Suppression increases excitability and its enhancement can silence neurons. We here show three five undergo strong their activity by oxidative modification induced physiological concentrations hydrogen peroxide. A triple cysteine pocket in channel S2–S3 linker is critical for this effect. Oxidation-induced produced a hyperpolarization dramatic reduction firing frequency rat sympathetic As peroxide robustly during hypoxia-induced stress, we used an oxygen/glucose deprivation neurodegeneration model showed death to be severely accelerated blockade. Such blockade had no effect on survival normoxic This work describes novel pathway M-channel regulation suggests role protective silencing stress.