Presynaptic mitochondria in functionally different motor neurons exhibit similar affinities for Ca2+ but exert little influence as Ca 2+ buffers at nerve firing rates in situ

Amit K. Chouhan, Jinhui Zhang, Konrad E. Zinsmaier, Gregory T. Macleod

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Mitochondria accumulate within nerve terminals and support synaptic function, most notably through ATP production. They can also sequester Ca 2+ during nerve stimulation, but it is unknown whether this limits presynaptic Ca2+ levels at physiological nerve firing rates. Similarly, it is unclear whether mitochondrial Ca2+ sequestration differs between functionally different nerve terminals. We addressed these questions using a combination of synthetic and genetically encoded Ca 2+ indicators to examine cytosolic and mitochondrial Ca2+ levels in presynaptic terminals of tonic (MN13-Ib) and phasic (MNSNb/d-Is) motor neurons in Drosophila, which, as we determined, fire during fictive locomotion at ∼42 Hz and ∼8 Hz, respectively. Mitochondrial Ca2+ sequestration starts in both terminals at ∼250 nM, exhibits a similar Ca2+-uptake affinity (∼410 nM), and does not require Ca 2+ release from the endoplasmic reticulum. Nonetheless, mitochondrial Ca2+ uptake in type Is terminals is more responsive to low-frequency nerve stimulation and this is due to higher cytosolic Ca2+ levels. Since type Ib terminals have a higher mitochondrial density than Is terminals, it seemed possible that greater mitochondrial Ca2+ sequestration may be responsible for the lower cytosolic Ca2+ levels in Ib terminals. However, genetic and pharmacological manipulations of mitochondrial Ca 2+ uptake did not significantly alter nerve-stimulated elevations in cytosolic Ca2+ levels in either terminal type within physiologically relevant rates of stimulation. Our findings indicate that presynaptic mitochondria have a similar affinity for Ca2+ in functionally different nerve terminals, but do not limit cytosolic Ca2+ levels within the range of motor neuron firing rates in situ.

Original languageEnglish (US)
Pages (from-to)1869-1881
Number of pages13
JournalJournal of Neuroscience
Volume30
Issue number5
DOIs
StatePublished - Feb 3 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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