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Published on: November 17, 2010
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
Summary
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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