Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction(719 views) Dolga AM, Netter MF, Perocchi F, Doti N, Meissner L, Tobaben S, Grohm J, Zischka H, Plesnila N, Decher N, Culmsee C
Institut fur Pharmakologie und Klinische Pharmazie, Fachbereich Pharmazie, Philipps-Universitat Marburg, D-35032 Marburg, Germany. dolga@staff.uni-marburg.de
Institut für Pharmakologie und Klinische Pharmazie, Fachbereich Pharmazie, Philipps-Universität Marburg, D-35032 Marburg, Germany
Institut für Physiologie und Pathophysiologie, Vegetative Physiologie, Fachbereich Medizin, D-35037 Marburg, Germany
Department of Systems Biology and Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States
Gene Center, Ludwig Maximilians University, Feodor-Lynen Strasse 25, 81377 Munich, Germany
Department of Neurodegeneration, Royal College of Surgeons in Ireland, Dublin 2, Ireland
Institute of Biostructures and Bioimaging, National Research Council (CNR), 16-80131 Naples, Italy
Institute of Stroke and Dementia Research, University of Munich Medical School, D-81377 Munich, Germany
Institute of Toxicology, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), D-85764 Neuherberg, Germany
Institut f r Pharmakologie und Klinische Pharmazie, Fachbereich Pharmazie, Philipps-Universit t Marburg, D-35032 Marburg, Germany
Institut f r Physiologie und Pathophysiologie, Vegetative Physiologie, Fachbereich Medizin, D-35037 Marburg, Germany
References: Not available.
Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction
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.
Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction
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Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction