Abstract
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 Mg 2+ block that reduces Ca 2+ 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.
Original language | English (US) |
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Pages (from-to) | 2302-2312 |
Number of pages | 11 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 31 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2011 |
Keywords
- cardiac arrest
- electrophysiology
- excitotoxicity
- global ischemia
- hippocampus
- potassium channels
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine