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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Mitochondrial small conductance SK2 channels prevent glutamate-induced oxytosis and mitochondrial dysfunction.
J. Biol. Chem. 288, 10792-10804 (2013)
Small conductance calcium-activated potassium (SK2/K(Ca)2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K+ currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Ca2+-activated K+ Channels ; Neuronal Cell-death ; Potassium Channels ; Atp Channel ; Provides Neuroprotection ; Integrative Genomics ; Therapeutic Targets ; Alzheimers-disease ; Cerebral-ischemia ; Calcium Uniporter
ISSN (print) / ISBN
0021-9258
e-ISSN
1083-351X
Zeitschrift
Journal of Biological Chemistry, The
Quellenangaben
Band: 288,
Heft: 15,
Seiten: 10792-10804
Verlag
American Society for Biochemistry and Molecular Biology
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed