Inhibition of mitochondrial Ca2+ uptake affects phasic release from motor terminals differently depending on external [Ca2+]

Janet D. Talbot, Gavriel David, Ellen Barrett

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We investigated how inhibition of mitochondrial Ca2+ uptake affects stimulation-induced increases in cytosolic [Ca2+] and phasic and asynchronous transmitter release in lizard motor terminals in 2 and 0.5 mM bath [Ca2+], Lowering bath [Ca2+] reduced the rate of rise, but not the final amplitude, of the increase in mitochondrial [Ca2+] during 50-Hz stimulation. The amplitude of the stimulation-induced increase in cytosolic [Ca2+] was reduced in low-bath [Ca2+] and increased when mitochondrial Ca2+ uptake was inhibited by depolarizing mitochondria. In 2 mM Ca2+, end-plate potentials (epps) depressed by 53% after 10 s of 50-Hz stimulation, and this depression increased to 80% after mitochondrial depolarization. In contrast, in 0.5 mM Ca2+ the same stimulation pattern increased epps by ∼3.4-fold, and this increase was even greater (transiently) after mitochondrial depolarization. In both 2 and 0.5 mM [Ca2+], mitochondrial depolarization increased asynchronous release during the 50-Hz train and increased the total vesicular release (phasic and asynchronous) measured by destaining of the styryl dye FM2-10. These results suggest that by limiting the stimulation-induced increase in cytosolic [Ca2+], mitochondrial Ca2+ uptake maintains a high ratio of phasic to asynchronous release, thus helping to sustain neuromuscular transmission during repetitive stimulation. Interestingly, the quantal content of the epp reached during 50-Hz stimulation stabilized at a similar level (∼20 quanta) in both 2 and 0.5 mM Ca2+. A similar convergence was measured in oligomycin, which inhibits mitochondrial ATP synthesis without depolarizing mitochondria, but quantal contents fell to <20 when mitochondria were depolarized in 2 mM Ca2+.

Original languageEnglish
Pages (from-to)491-502
Number of pages12
JournalJournal of Neurophysiology
Volume90
Issue number1
StatePublished - Jul 1 2003

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Excitatory Postsynaptic Potentials
Baths
Mitochondria
Oligomycins
Lizards
Coloring Agents
Adenosine Triphosphate

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Inhibition of mitochondrial Ca2+ uptake affects phasic release from motor terminals differently depending on external [Ca2+]. / Talbot, Janet D.; David, Gavriel; Barrett, Ellen.

In: Journal of Neurophysiology, Vol. 90, No. 1, 01.07.2003, p. 491-502.

Research output: Contribution to journalArticle

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