Mitochondrial small conductance SK2 channels prevent glutamate-induced oxytosis and mitochondrial dysfunction

Amalia M Dolga, Michael F Netter, Fabiana Perocchi, Nunzianna Doti, Lilja Meissner, Svenja Tobaben, Julia Grohm, Hans Zischka, Nikolaus Plesnila, Niels Decher, Carsten Culmsee

Research output: Contribution to journalArticleAcademicpeer-review

63 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10792-10804
Number of pages13
JournalThe Journal of Biological Chemistry
Volume288
Issue number15
DOIs
Publication statusPublished - 12-Apr-2013
Externally publishedYes

Keywords

  • Animals
  • Cell Line
  • Cell Membrane
  • Glutamic Acid
  • Membrane Potential, Mitochondrial
  • Mice
  • Mitochondria
  • Mitochondrial Membranes
  • Nerve Tissue Proteins
  • Neurons
  • Neuroprotective Agents
  • Peptides
  • Potassium
  • Small-Conductance Calcium-Activated Potassium Channels

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