K+ depolarization evokes ATP, adenosine and glutamate release from glia in rat hippocampus: A microelectrode biosensor study

A. Heinrich, R. D. Andõ, G. Túri, B. Rõzsa, B. Sperlágh

Research output: Contribution to journalReview article

44 Citations (Scopus)

Abstract

Background and purpose: This study was undertaken to characterize the ATP, adenosine and glutamate outflow evoked by depolarization with high K+ concentrations, in slices of rat hippocampus. Experimental approach: We utilized the microelectrode biosensor technique and extracellular electrophysiological recording for the real-time monitoring of the efflux of ATP, adenosine and glutamate. Key results: ATP, adenosine and glutamate sensors exhibited transient and reversible current during depolarization with 25 mM K+, with distinct kinetics. The ecto-ATPase inhibitor ARL67156 enhanced the extracellular level of ATP and inhibited the prolonged adenosine efflux, suggesting that generation of adenosine may derive from the extracellular breakdown of ATP. Stimulation-evoked ATP, adenosine and glutamate efflux was inhibited by tetrodotoxin, while exposure to Ca2+-free medium abolished ATP and adenosine efflux from hippocampal slices. Extracellular elevation of ATP and adenosine were decreased in the presence of NMDA receptor antagonists, D-AP-5 and ifenprodil, whereas non-NMDA receptor blockade by CNQX inhibited glutamate but not ATP and adenosine efflux. The gliotoxin fluoroacetate and P2X7 receptor antagonists inhibited the K+-evoked ATP, adenosine and glutamate efflux, while carbenoxolone in low concentration and probenecid decreased only the adenosine efflux. Conclusions and implications: Our results demonstrated activity-dependent gliotransmitter release in the hippocampus in response to ongoing neuronal activity. ATP and glutamate were released by P2X7 receptor activation into extracellular space. Although the increased extracellular levels of adenosine did derive from released ATP, adenosine might also be released directly via pannexin hemichannels.

Original languageEnglish
Pages (from-to)1003-1020
Number of pages18
JournalBritish journal of pharmacology
Volume167
Issue number5
DOIs
Publication statusPublished - Nov 1 2012

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Keywords

  • ATP
  • K depolarization
  • adenosine
  • connexin
  • glia
  • glutamate
  • hippocampus
  • pannexin
  • release

ASJC Scopus subject areas

  • Pharmacology

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