Extrusion of Ca2+ from mouse motor terminal mitochondria via a Na+-Ca2+ exchanger increases post-tetanic evoked release

Luis Ernesto Garcia-Chacon, Khanh T. Nguyen, Gavriel David, Ellen F. Barrett

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Mitochondria sequester much of the Ca2+ that enters motor nerve terminals during repetitive stimulation at frequencies exceeding 10-20 Hz. We studied the post-stimulation extrusion of Ca2+ from mitochondria by measuring changes in matrix [Ca2+] with fluorescent indicators loaded into motor terminal mitochondria in the mouse levator auris longus muscle. Trains of action potentials at 50 Hz produced a rapid increase in mitochondrial [Ca2+] followed by a plateau, which was usually maintained after the end of the stimulus train and then slowly decayed back to baseline. Increasing the Ca2+ load delivered to the terminal by increasing the number of stimuli (from 500 to 2000) or the stimulation frequency (from 50 to 100 Hz), by increasing bath [Ca2+], or by prolonging the action potential with 3,4-diaminopyridine (100 μM) prolonged the post-stimulation decay of mitochondrial [Ca2+] without increasing the amplitude of the plateau during stimulation. Inhibiting the opening of the mitochondrial permeability transition pore with cyclosporin A (5 μM) had no significant effect on the decay of mitochondrial [Ca2+]. Inhibition of the mitochondrial Na+-Ca2+ exchanger with CGP-37157 (50 μM) dramatically prolonged the post-stimulation decay of mitochondrial [Ca2+], reduced post-stimulation residual cytosolic [Ca2+], and reduced the amplitude of endplate potentials evoked after the end of a stimulus train in the presence of both low and normal bath [Ca2+]. These findings suggest that Ca2+ extrusion from motor terminal mitochondria occurs primarily via the mitochondrial Na+-Ca2+ exchanger and helps to sustain post-tetanic transmitter release at mouse neuromuscular junctions.

Original languageEnglish (US)
Pages (from-to)663-675
Number of pages13
JournalJournal of Physiology
Volume574
Issue number3
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Physiology

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