Effects of Extracellular pH on the Dynorphin A Inhibition of N-Methyl-D-Aspartate Receptors Expressed in Xenopus Oocytes

Murat Oz, Amina S. Woods, Toni Shippenberg, Rafal M. Kaminski

Research output: Contribution to journalArticle

Abstract

Dynorphin A (Dyn A) (1-17), the postulated endogenous ligand for the κ-opioid receptor, inhibits N-methyl-D-aspartate (NMDA) receptor-mediated currents in neuronal preparations and in Xenopus oocytes expressing recombinant NMDA receptors. Although direct interactions of Dyn A with the NMDA receptor have been reported, the mechanisms mediating the inhibitory actions of Dyn A are unknown. Extracellular pH is a crucial factor regulating NMDA receptor function. To date, however, the influence of pH on the inhibitory actions of Dyn A has not been examined. In the present study we used voltage-clamp recording techniques in Xenopus oocytes expressing recombinant NR1A/2A receptors to address this issue. We report that decreasing the pH of the external solution from 7.5 to 6.7 significantly enhances Dyn A inhibition of NMDA receptor-mediated currents. On the contrary, increasing the pH of the external solution to 9.2 prevents the inhibitory action of Dyn A. The influence of external pH was independent of membrane potential and the potentiation of inhibition with decreasing pH was not associated with alterations in the charge of the Dyn A molecule. These findings demonstrate that Dyn A inhibition of the NMDA receptor current is pH-dependent. They further suggest that the efficacy of neuronally released Dyn A in inhibiting NMDA receptor function may be increased in response to nerve injury and other conditions associated with decreased extracellular pH.

Original languageEnglish (US)
Pages (from-to)84-88
Number of pages5
JournalSynapse
Volume52
Issue number2
DOIs
StatePublished - May 2004
Externally publishedYes

Keywords

  • Dynorphin
  • Glutamate receptor
  • N-methyl-D-aspartate receptor
  • Proton
  • Xenopus oocyte

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

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