Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel

Kunjan R. Dave, Richard Anthony Defazio, Ami P. Raval, Oleksandr Dashkin, Isabel Saul, Kimberly E. Iceman, Miguel A. Perez-Pinzon, Kelly L. Drew

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

During the pre-hibernation season, arctic ground squirrels (AGS) can tolerate 8 min of asphyxial cardiac arrest (CA) without detectable brain pathology. Better understanding of the mechanisms regulating innate ischemia tolerance in AGS has the potential to facilitate the development of novel prophylactic agents to induce ischemic tolerance in patients at risk of stroke or CA. We hypothesized that neuroprotection in AGS involves robust maintenance of ion homeostasis similar to anoxia-tolerant turtles. Ion homeostasis was assessed by monitoring ischemic depolarization (ID) in cerebral cortex during CA in vivo and during oxygen glucose deprivation in vitro in acutely prepared hippocampal slices. In both models, the onset of ID was significantly delayed in AGS compared with rats. The epsilon protein kinase C (ηPKC) is a key mediator of neuroprotection and inhibits both Na+/K +-ATPase and voltage-gated sodium channels, primary mediators of the collapse of ion homeostasis during ischemia. The selective peptide inhibitor of ηPKC (ηV1-2) shortened the time to ID in brain slices from AGS but not in rats despite evidence that ηV1-2 decreased activation of ηPKC in brain slices from both rats and AGS. These results support the hypothesis that ηPKC activation delays the collapse of ion homeostasis during ischemia in AGS.

Original languageEnglish (US)
Pages (from-to)1170-1179
Number of pages10
JournalJournal of neurochemistry
Volume110
Issue number4
DOIs
StatePublished - Aug 2009

Keywords

  • Brain ischemia
  • Heart arrest
  • Neuroprotection
  • Tolerance

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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