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 Adelman, Paco S. Herson

Research output: Contribution to journalArticle

46 Citations (Scopus)

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

Fingerprint

Cardiopulmonary Resuscitation
Cell Death
Ischemia
Heart Arrest
N-Methyl-D-Aspartate Receptors
Brain Ischemia
Calcium-Activated Potassium Channels
Induced Heart Arrest
Immunoelectron Microscopy
Pyramidal Cells
Neuroprotective Agents
Neurons
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Allen, D., Nakayama, S., Kuroiwa, M., Nakano, T., Palmateer, J., Kosaka, Y., ... 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

SK2 channels are neuroprotective for ischemia-induced neuronal cell death. / Allen, Duane; Nakayama, Shin; Kuroiwa, Masayuki; Nakano, Takaaki; Palmateer, Julie; Kosaka, Yasuharu; Ballesteros, Carmen; Watanabe, Masahiko; Bond, Chris T.; Luján, Rafael; Maylie, James; Adelman, John; Herson, Paco S.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 31, No. 12, 12.2011, p. 2302-2312.

Research output: Contribution to journalArticle

Allen, D, Nakayama, S, Kuroiwa, M, Nakano, T, Palmateer, J, Kosaka, Y, Ballesteros, C, Watanabe, M, Bond, CT, Luján, R, Maylie, J, Adelman, J & Herson, PS 2011, 'SK2 channels are neuroprotective for ischemia-induced neuronal cell death', Journal of Cerebral Blood Flow and Metabolism, vol. 31, no. 12, pp. 2302-2312. https://doi.org/10.1038/jcbfm.2011.90
Allen, Duane ; Nakayama, Shin ; Kuroiwa, Masayuki ; Nakano, Takaaki ; Palmateer, Julie ; Kosaka, Yasuharu ; Ballesteros, Carmen ; Watanabe, Masahiko ; Bond, Chris T. ; Luján, Rafael ; Maylie, James ; Adelman, John ; Herson, Paco S. / SK2 channels are neuroprotective for ischemia-induced neuronal cell death. In: Journal of Cerebral Blood Flow and Metabolism. 2011 ; Vol. 31, No. 12. pp. 2302-2312.
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