Opening of ATP-sensitive potassium channels by cromakalim confers tolerance against chemical ischemia in rat neuronal cultures

Ayelet Reshef, Oded Sperling*, Esther Zoref-Shani

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

The effect of opening and of blocking of ATP-sensitive potassium (K(ATP)) channels on the short-term capacity of neurons to resist ischemia- reperfusion-induced cell injury, was studied in a model of primary rat neuronal cultures, subjected to metabolic poisoning by iodoacetic acid (150 μM, 150 min), followed by reperfusion (1 h). The metabolic poisoning resulted in a marked decrease in cellular ATP content (from 65.3 ±13.4 to 21.6 ± 11.7 nmole/mg protein), simulating an ischemia, or hypoxiainduced condition of energy crisis. The degree of neuronal damage was assessed by the trypan blue exclusion test. Exposure of the neurons to the channel-opener cromakalim (10 μM; 15 min), prior to the insult, induced resistance, which could be abolished by the specific channel blocker glibenclamide (2 μM). Glibenclamide also abolished the protection acquired by preconditioning of the neurons with iodoacetate (IA; 100 μM), the adenosine A1 agonist N6-(R)- phenylisopropyladenosine (R-PIA; 100 μM), or with the protein kinase C (PKC) activator 1,2 dioctanoyl-rac-glycerol (dog; 1 μM). The results indicate that in the neurons, opening of the K(ATP) channels confers protection against an ATP-depleting crisis, and suggest that the protective effects induced by adenosine and by activation of PKC, are mediated by the opening of these channels.

Original languageEnglish
Pages (from-to)111-114
Number of pages4
JournalNeuroscience Letters
Volume250
Issue number2
DOIs
StatePublished - 19 Jun 1998

Keywords

  • 1,2 Dioctanoyl- rac-glycerol
  • ATP-sensitive potassium channels
  • Adenosin
  • Cromakalim
  • Glibenclamide
  • Ischemia-reperfusion damage
  • Ischemic tolerance
  • N6- (R)-phenylisopropyladenosine
  • Neuronal cultures

Fingerprint

Dive into the research topics of 'Opening of ATP-sensitive potassium channels by cromakalim confers tolerance against chemical ischemia in rat neuronal cultures'. Together they form a unique fingerprint.

Cite this