Extracellular calcium depletion transiently elevates oxygen consumption in neurosecretory PC12 cells through activation of mitochondrial Na + /Ca 2+ exchange

Alexander V. Zhdanov*, Manus Ward, Cormac T. Taylor, Ekaterina A. Souslova, Dmitri M. Chudakov, Jochen H.M. Prehn, Dmitri B. Papkovsky

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    22 Scopus citations

    Abstract

    Fluctuating extracellular Ca 2+ regulates many aspects of neuronal (patho)physiology including cell metabolism and respiration. Using fluorescence-based intracellular oxygen sensing technique, we demonstrate that depletion of extracellular Ca 2+ from 1.8 to ≤0.6mM by chelation with EGTA induces a marked spike in O 2 consumption in differentiated PC12 cells. This respiratory response is associated with the reduction in cytosolic and mitochondrial Ca 2+ , minor depolarization on the mitochondrial membrane, moderate depolarization of plasma membrane, and no changes in NAD(P)H and ATP. The response is linked to the influx of extracellular Na + and the subsequent activation of mitochondrial Na + /Ca 2+ and Na + /H + exchange. The mitochondrial Na + /Ca 2+ exchanger ( m NCX) activated by Na + influx reduces Ca 2+ and increases Na + levels in the mitochondrial matrix. The excess of Na + activates the mitochondrial Na + /H + exchanger (NHE) increasing the outward pumping of protons, electron transport and O 2 consumption. Reduction in extracellular Na + and inhibition of Na + influx through the receptor operated calcium channels and plasmalemmal NHE reduce the respiratory response. Inhibition of the m NCX, L-type voltage gated Ca 2+ channels or the release of Ca 2+ from the endoplasmic reticulum also reduces the respiratory spike, indicating that unimpaired intercompartmental Ca 2+ exchange is critical for response development.

    Original languageEnglish (US)
    Pages (from-to)1627-1637
    Number of pages11
    JournalBiochimica et Biophysica Acta - Bioenergetics
    Volume1797
    Issue number9
    DOIs
    StatePublished - Sep 1 2010

    Keywords

    • Cell Metabolism
    • Extracellular calcium
    • Intracellular calcium
    • Mitochondria
    • Phosphorescent Oxygen-Sensitive Probe
    • Respiration

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Cell Biology

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