Ischemic preconditioning in the hippocampus of a knockout mouse lacking SUR1-based KATP channels

Alvaro Muñoz, Mitsuhiro Nakazaki, J. Clay Goodman, Roberto Barrios, Carlos G. Onetti, Joseph Bryan, Lydia Aguilar-Bryan

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Background and Purpose - ATP-sensitive K+ (KATP channels have been implicated in the mechanism of neuronal ischemic preconditioning. To evaluate the role of neuronal/β-cell-type KATP channels, SUR1 null (Sur1 KO) mice lacking (KIR6.x/SUR1)4 KATP channels were subjected to a preconditioning protocol with the use of double carotid occlusion. Methods - Wild-type C57BL/6 and Sur1 KO mice were subjected to a double carotid block for 40 minutes with or without a 20-minute preconditioning block. After a 10-day reperfusion period, damage was assessed histologically in the hippocampal CA1, CA2, and CA3 areas and in the dentate gyrus. The neuroprotective effects of intracerebroventricular injections of diazoxide, which selectively affects mitochondria versus opening SUR1-type KATP channels, and 5-hydroxydecanoate, a selective blocker of mitoKATP channels, were evaluated with the same protocol. Results - Neurons in the CA1 region of both Sur1 KO and wild-type animals subjected to a 20-minute ischemic insult were protected equally from neuronal damage produced by a subsequent 40-minute ischemic period. Pretreatment with diazoxide protected both Sur1 KO and wild-type neurons, while 5-hydroxydecanoate augmented neurodegeneration in both strains of animals when administered before a 20-minute bout of ischemia. Conclusions - SUR1-based KATP channels are not obligatory for neuronal preconditioning or augmentation of neurodegeneration by 5-hydroxydecanoate.

Original languageEnglish (US)
Pages (from-to)164-170
Number of pages7
JournalStroke
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Cerebral ischemia
  • Decanoic acids
  • Diazoxide
  • Hippocampus
  • Ischemic preconditioning
  • Mice
  • Potassium channels
  • Sulfonylurea receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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