Mechanisms of injury-induced calcium entry into peripheral nerve myelinated axons: Role of reverse sodium-calcium exchange

Ellen J. Lehning, Renu Doshi, Norman Isaksson, Peter K. Stys, Richard M. LoPachin

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


To investigate the route of axonal Ca2+ entry during anoxia, electron probe x-ray microanalysis was used to measure elemental composition of anoxic tibial nerve myelinated axons after in vitro experimental procedures that modify transaxolemmal Na+ and Ca2+ movements. Perfusion of nerve segments with zero-Na+/Li+-substituted medium and Na+ channel blockade by tetrodotoxin (1 μM) prevented anoxia-induced increases in Na and Ca concentrations of axoplasm and mitochondria. Incubation with a zero- Ca2+/EGTA perfusate impeded axonal and mitochondrial Ca accumulation during anoxia but did not affect characteristic Na and K responses. Inhibition of Na+-Ca2+ exchange with bepridil (50 μM) reduced significantly the Ca content of anoxio axons although mitochondrial Ca remained at anoxic levels. Nifedipine (10 μM), an L-type Ca2+ channel blocker, did not alter anoxia- induced changes in axonal Na, Ca, and K. Exposure of normoxic control nerves to tetrodotoxin, bepridil, or nifedipine did not affect axonal elemental composition, whereas both zero-Ca2+ and zero-Na+ solutions altered normal elemental content characteristically and significantly. The findings of this study suggest that during anoxia, Na+ enters axons via voltage-gated Na+ channels and that subsequent increases in axoplasmic Na+ are coupled functionally to extraaxonal Ca2+ import. Intracellular Na+-dependent, extraaxonal Ca2+ entry is consistent with reverse operation of the axolemmal Na+-Ca2+ exchanger, and we suggest that this mode of Ca2+ influx plays a general role in peripheral nerve axon injury.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalJournal of Neurochemistry
Issue number2
StatePublished - Feb 1996


  • Acrylamide
  • Anoxia
  • Electron probe x-ray microanalysis
  • Myelinated axons
  • Na-Ca exchanger
  • Peripheral nerve

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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