SK2 channels are neuroprotective for ischemia-induced neuronal cell death

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

Research output: Contribution to journalArticle

50 Scopus citations

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 languageEnglish (US)
Pages (from-to)2302-2312
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • cardiac arrest
  • electrophysiology
  • excitotoxicity
  • global ischemia
  • hippocampus
  • potassium channels

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Allen, D., Nakayama, S., Kuroiwa, M., Nakano, T., Palmateer, J., Kosaka, Y., Ballesteros, C., Watanabe, M., Bond, C. T., Luján, R., Maylie, J., Adelman, J. P., & Herson, P. S. (2011). SK2 channels are neuroprotective for ischemia-induced neuronal cell death. Journal of Cerebral Blood Flow and Metabolism, 31(12), 2302-2312. https://doi.org/10.1038/jcbfm.2011.90