PubMed 21712833

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: SK2

Title: SK2 channels are neuroprotective for ischemia-induced neuronal cell death.

Authors: Duane Allen, Shin Nakayama, Masayuki Kuroiwa, Takaaki Nakano, Julie Palmateer, Yasuharu Kosaka, Carmen Ballesteros, Masahiko Watanabe, Chris T Bond, Rafael Lujan, James Maylie, John P Adelman, Paco S Herson

Journal, date & volume: J. Cereb. Blood Flow Metab., 2011 Dec , 31, 2302-12

PubMed link:

In mouse hippocampal CA1 pyramidal neurons, the activity of synaptic small-conductance Ca(2+)-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.