NMDA-evoked consumption and recovery of mitochondrially targeted aequorin suggests increased Ca2+ uptake by a subset of mitochondria in hippocampal neurons

Kyle T. Baron, Guang Jian Wang, Rodolfo A. Padua, Colin R Campbell, Stanley A Thayer

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Activation of NMDA receptors produces large increases in cytosolic Ca 2+ that are taken up into mitochondria. We used recombinant aequorin targeted to mitochondria to report changes in matrix Ca2+ in rat hippocampal neurons in culture. Upon binding Ca2+, aequorin emits a photon in a one-shot reaction that consumes the indicator. Here we show that stimulation with NMDA produced a mitochondrial Ca2+ response that rapidly inactivated. However, following a 30-min recovery period the response was restored, suggesting the presence of a pool of indicator that was not exposed to high Ca2+ during the initial stimulus. We speculate that aequorin distant from the Ca2+ source was protected from microdomains of high Ca2+ near the plasmalemma and that this aequorin moved, either by movement of individual mitochondria or via the mitochondrial tubular network, to replenish consumed indicator during the recovery time. A large Ca2+ increase in a subset of mitochondria could produce local changes in energy metabolism, regional Ca2+ buffering, and foci that initiate neurotoxic processes.

Original languageEnglish (US)
Pages (from-to)124-132
Number of pages9
JournalBrain Research
Volume993
Issue number1-2
DOIs
StatePublished - Dec 12 2003

Keywords

  • Aequorin
  • Ca microdomains
  • Excitotoxicity
  • Mitochondria
  • NMDA
  • [Ca]

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