Effects of ATP-sensitive potassium channel activators diazoxide and BMS-191095 on membrane potential and reactive oxygen species production in isolated piglet mitochondria

David W. Busija, Prasad Katakam, Nishadi C. Rajapakse, Bela Kis, Gary Grover, Ferenc Domoki, Ferenc Bari

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Mitochondrial ATP-sensitive potassium (mitoKATP) channel openers protect the piglet brain against ischemic stress. Effects of mitoK ATP channel agonists on isolated mitochondria, however, have not been directly examined. We investigated the effects of KATP channel openers and blockers on membrane potential and on the production of reactive oxygen species (ROS) in isolated piglet mitochondria. Diazoxide and BMS-191095, putative selective openers of mitoKATP, decreased the mitochondrial membrane potential (ΔΨm). On a molar basis, diazoxide was less effective than BMS-191095. In contrast, diazoxide but not BMS-191095 increased ROS production by mitochondria. Since diazoxide also inhibits succinate dehydrogenase (SDH), we examined the effects of 3-nitropropionic acid (3-NPA), an inhibitor of SDH. 3-NPA failed to change the ΔΨ m but increased ROS production. Inhibitors of KATP channels did not affect resting ΔΨm or ROS production, but glibenclamide and 5-hydroxydecanoate (5-HD) blocked effects of diazoxide and BMS-191095 on ΔΨm and diazoxide effects on ROS production. We conclude that BMS-191095 has selective effects on mitoKATP channels while diazoxide also increases ROS production probably via inhibition of SDH.

Original languageEnglish
Pages (from-to)85-90
Number of pages6
JournalBrain Research Bulletin
Volume66
Issue number2
DOIs
Publication statusPublished - Jul 30 2005

    Fingerprint

Keywords

  • BMS-191095
  • Diazoxide
  • Inwardly rectifying potassium channel
  • Ischemia
  • Mitochondria
  • Potassium channels
  • Succinate dehydrogenase
  • Sulfonylurea receptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this