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

Nikita Gamper, Oleg Zaika, Yang Li, Pamela Martin, Ciria C. Hernandez, Michael R. Perez, Andrew Y.C. Wang, David B. Jaffe, Mark S. Shapiro

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4996-5004
Number of pages9
JournalEMBO Journal
Issue number20
StatePublished - Oct 18 2006


  • Cysteine
  • KCNQ
  • Kv7
  • Neurodegeneration
  • ROS

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • Molecular Biology
  • General Neuroscience


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