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Oxidative modification of M‐type K + channels as a mechanism of cytoprotective neuronal silencing
Author(s) -
Gamper Nikita,
Zaika Oleg,
Li Yang,
Martin Pamela,
Hernandez Ciria C,
Perez Michael R,
Wang Andrew YC,
Jaffe David B,
Shapiro Mark S
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601374
Subject(s) - library science , health science , gerontology , physiology , biology , medicine , computer science , medical education
Voltage‐gated K + channels of the Kv7 family underlie the neuronal M current that regulates action potential firing. Suppression of M current increases excitability and its enhancement can silence neurons. We here show that three of five Kv7 channels undergo strong enhancement of their activity by oxidative modification induced by physiological concentrations of hydrogen peroxide. A triple cysteine pocket in the channel S2–S3 linker is critical for this effect. Oxidation‐induced enhancement of M current produced a hyperpolarization and a dramatic reduction of action potential firing frequency in rat sympathetic neurons. As hydrogen peroxide is robustly produced during hypoxia‐induced oxidative stress, we used an oxygen/glucose deprivation neurodegeneration model that showed neuronal death to be severely accelerated by M current blockade. Such blockade had no effect on survival of normoxic neurons. This work describes a novel pathway of M‐channel regulation and suggests a role for M channels in protective neuronal silencing during oxidative stress.