Mitochondrial clearance of cytosolic Ca2+ in stimulated lizard motor nerve terminals proceeds without progressive elevation of mitochondrial matrix [Ca2+]

Gavriel David

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


This study used fluorescent indicator dyes to measure changes in cytosolic and mitochondrial [Ca2+] produced by physiological stimulation of lizard motor nerve terminals. During repetitive action potential discharge at 10-50 Hz, the increase in average cytosolic [Ca2+] reached plateau at levels that increased with increasing stimulus frequency. This stabilization of cytosolic [Ca2+] was caused mainly by mitochondrial Ca2+ uptake, because drugs that depolarize mitochondria greatly increased the stimulation- induced elevation of cytosolic [Ca2+], whereas blockers of other Ca2+ clearance routes had little effect. Surprisingly, during this sustained Ca2+ uptake the free [Ca2+] in the mitochondrial matrix never exceeded a plateau level of ~1 μM, regardless of stimulation frequency or pattern. When stimulation ceased, matrix [Ca2+] decreased over a slow (~10 min) time course consisting of an initial plateau followed by a return to baseline. These measurements demonstrate that sustained mitochondrial Ca2+ uptake is not invariably accompanied by progressive elevation of matrix free [Ca2+]. Both the plateau of matrix free [Ca2+] during stimulation and its complex decay after stimulation could be accounted for by a model incorporating reversible formation of an insoluble Ca salt. This mechanism allows mitochondria to sequester large amounts of Ca2+ while maintaining matrix free [Ca2+] at levels sufficient to activate Ca2+-dependent mitochondrial dehydrogenases, but below levels that activate the permeability transition pore.

Original languageEnglish (US)
Pages (from-to)7495-7506
Number of pages12
JournalJournal of Neuroscience
Issue number17
StatePublished - Sep 1 1999


  • Calcium buffering
  • Calcium indicator dyes
  • Calcium sequestration
  • Mitochondria
  • Mitochondrial calcium uptake
  • Mitochondrial matrix
  • Motor nerve terminal
  • Presynaptic terminal

ASJC Scopus subject areas

  • Neuroscience(all)


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