SK2 Channels Are Neuroprotective for Ischemia-Induced Neuronal Cell Death
Copyright policy )SK2 Channels Are Neuroprotective for Ischemia-Induced Neuronal Cell Death
In mouse hippocampal CA1 pyramidal neurons, the activity of synaptic small-conductance Ca2+-activated K+ channels type 2 (SK2 channels) provides a negative feedback on N-methyl-d-aspartate receptors (NMDARs), reestablishing Mg2+ block that reduces Ca2+ influx. The well-established role of NMDARs in ischemia-induced excitotoxicity led us to test the neuroprotective effect of modulating SK2 channel activity following cerebral ischemia induced by cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Administration of the SK channel positive modulator, 1-ethyl-benzimidazolinone (1-EBIO), significantly reduced CA1 neuron cell death and improved CA/CPR-induced cognitive outcome. Electrophysiological recordings showed that CA/CPR-induced ischemia caused delayed and sustained reduction of synaptic SK channel activity, and immunoelectron microscopy showed that this is associated with internalization of synaptic SK2 channels, which was prevented by 1-EBIO treatment. These results suggest that increasing SK2 channel activity, or preventing ischemia-induced loss of synaptic SK2 channels, are promising and novel approaches to neuroprotection following cerebral ischemia.
- Vollum Institute United States
- Hokkaido Bunkyo University Japan
- University of Castile-La Mancha Spain
- Hokkaido University Japan
- Oregon Health & Science University United States
Male, Neurons, Patch-Clamp Techniques, Behavior, Animal, Cell Death, Pyramidal Cells, Mice, Transgenic, Recognition, Psychology, In Vitro Techniques, Motor Activity, Immunohistochemistry, Cardiopulmonary Resuscitation, Brain Ischemia, Heart Arrest, Mice, Inbred C57BL, Mice, Animals, Benzimidazoles, Microscopy, Immunoelectron, CA1 Region, Hippocampal
Male, Neurons, Patch-Clamp Techniques, Behavior, Animal, Cell Death, Pyramidal Cells, Mice, Transgenic, Recognition, Psychology, In Vitro Techniques, Motor Activity, Immunohistochemistry, Cardiopulmonary Resuscitation, Brain Ischemia, Heart Arrest, Mice, Inbred C57BL, Mice, Animals, Benzimidazoles, Microscopy, Immunoelectron, CA1 Region, Hippocampal
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