Inhibition of energy metabolism by 3-nitropropionic acid activates ATP-sensitive potassium channels

Matthias Riepe, Nobuaki Hori, Albert C. Ludolph, David O. Carpenter, Peter S. Spencer, Charles N. Allen

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

3-Nitropropionic acid (1 mM), which inhibits succinate dehydrogenase activity and reduces cellular energy, produces in the pyramidal cell layer of the hippocampal region CAl a hyperpolarization for variable lengths of time before evoking an irreversible depolarization. Hyperpolarization is caused by an increased potassium conductance that is attenuated by glibenclamide (1-10 μM), a selective antagonist of ATP-sensitive potassium channels: in contrast,diazoxide (0.5 mM), an agonist at this channel, induces a hyperpolarization in CA1 neurons of rat hippocampal slices. The transient hyperpolarization after prolonged (ca. 1 h) application of 3 NPA is followed by a depolarization that incompletely reversed by brief application of the glutamate antagonists (d-2-amino-5-phosphonopentanoic acid (APV), 6,7-dichloroquinoxaline-2,3-dione (CNQX), 3-(±)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), 7-chloro-kynurenic acid (7Cl-KYN)). Early application of glibenclamide (within the initial 5 min) blocked or reduced hyperpolarization and accelerated the depolarization. These data suggest that metabolic inhibition by 3-NPA initially activates ATP-sensitive potassium channels. Events other than activation of glutamate receptors participate in the final depolarization resulting from uncoupling of oxidative phosphorylation.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalBrain research
Volume586
Issue number1
DOIs
StatePublished - Jul 17 1992

Keywords

  • 3-Nitropropionic acid (3-NPA)
  • ATP
  • Diazoxide
  • Glibenclamide
  • Glutamate antagonists
  • Histotoxic hypoxia
  • Oxidative phosphorylation
  • Potassium channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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