Oxidative modification of M-type K+ channels as a mechanism of cytoprotective neuronal silencing
| Autor: | David B. Jaffe, Nikita Gamper, Yang Li, Ciria C. Hernandez, Michael R Perez, Oleg Zaika, Mark S. Shapiro, Andrew Y C Wang, Pamela M. Martin |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cell Survival
Models Neurological CHO Cells Oxidative phosphorylation Biology medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Membrane Potentials chemistry.chemical_compound Cricetulus Cricetinae M current medicine Animals Humans Gene silencing Gene Silencing Hydrogen peroxide Molecular Biology Neurons Membrane potential Dose-Response Relationship Drug KCNQ Potassium Channels General Immunology and Microbiology General Neuroscience Neurodegeneration Neurodegenerative Diseases Hydrogen Peroxide Hyperpolarization (biology) Oxidants medicine.disease Cell Hypoxia Rats Oxidative Stress Glucose nervous system Biochemistry chemistry Sweetening Agents Biophysics Oxidation-Reduction Oxidative stress |
| Zdroj: | The EMBO Journal. 25:4996-5004 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7601374 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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