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Presynaptic function is altered in snake K+-depolarized motor nerve terminals containing compromised mitochondria

M A Calupca1, C Prior, L A Merriam

  • 1Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT 05405, USA.

The Journal of Physiology
|April 3, 2001
PubMed

Insights

Energy depletion impairs nerve terminal function. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) and oligomycin treatments reduce ATP, leading to elevated intracellular calcium and decreased neurotransmitter release during sustained nerve stimulation.

Area of Science:

  • Neuroscience
  • Cellular Physiology
  • Synaptic Transmission

Background:

  • Presynaptic function relies on energy-dependent processes for neurotransmitter release and vesicle recycling.
  • Mitochondrial inhibitors like carbonyl cyanide m-chlorophenylhydrazone (CCCP) and oligomycin disrupt cellular energy production.
  • Sustained neuronal activity requires efficient ATP supply to maintain homeostasis and synaptic function.

Purpose of the Study:

  • To investigate the impact of energy depletion on presynaptic function in K+-stimulated motor nerve terminals.
  • To elucidate the role of intracellular calcium ([Ca2+]i) and ATP levels in neurotransmitter release during metabolic stress.
  • To examine the effects of CCCP and oligomycin on synaptic vesicle endocytosis and quantal release.

Main Methods:

  • Electrophysiological recordings of miniature endplate currents (MEPCs) in snake motor nerve terminals.
  • Application of K+ stimulation (35 mM) in the presence of metabolic inhibitors (CCCP, oligomycin).
  • FM1-43 fluorescence imaging to assess synaptic vesicle endocytosis.

Main Results:

  • CCCP and oligomycin treatments, individually or combined, initially increased MEPC frequency but subsequently caused a decline.
  • The decline in MEPC frequency was accelerated by CCCP, suggesting impaired mitochondrial function.
  • Energy depletion led to reduced synaptic vesicle endocytosis, which was partially rescued by glucose addition.

Conclusions:

  • Progressive elevation of intracellular calcium ([Ca2+]i) due to impaired ATP production and buffering contributes to the decline in quantal release.
  • Mitochondrial dysfunction exacerbates calcium dysregulation and accelerates the failure of presynaptic function.
  • Maintaining ATP levels via glycolysis can partially mitigate the negative effects of energy depletion on synaptic transmission.

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