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

Michelle A. Calupca, Chris Prior, Laura A. Merriam, Gregory M. Hendricks, Rodney L. Parsons

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Presynaptic function was investigated at K+-stimulated motor nerve terminals in snake costocutaneous nerve muscle preparations exposed to carbonyl cyanide m-chlorophenly- hydrazone (CCCP, 2 muM), oligomycin (8 mug ml(-1)) or CCCP and oligomycin together. Miniature endplate currents (MEPCs) R ere recorded at -150 mV with two-electrode voltage clamp. With all three drug treatments, during stimulation by elevated K+ (35 mM), MEPC frequencies initially increased to values > 350 s(-1), hut then declined. The decline occurred more rapidly in preparations treated with CCCP or CCCP and oligomycin together than in those treated with oligomycin alone. Staining with FM1-43 indicated that synaptic vesicle membrane endocytosis occurred at some CCCP- or oligomycin-treated nerve terminals after 120 or 180 min of K+ stimulation, respectively. The addition of glucose to stimulate production of ATP bp glycolysis during sustained K+ stimulation attenuated the decline in MEPC frequency) and increased the percentage of terminals stained by FM1-43 in preparations exposed to either CCCP or oligomycin. We propose that the decline in K+-stimulated quantal release in preparations treated with CCCP, oligomycin or CCCP and oligomycin together could result from a progressive elevation of intracellular calcium concentration ([Ca2+](1)). For oligomycin-treated nerve terminals, a progressive elevation of [Ca2+](1) could occur as the cytoplasmic ATP/ADP ratio decreases, causing energy-dependent Ca2+ buffering mechanisms to fail. The decline in MEPC frequency could occur more rapidly in preparations treated with CCCP or CCCP and oligomycin together because mitochondrial Ca2+ buffering and ATP production a ere both inhibited. Therefore, the proposed sustained elevation of [Ca2+](1) could occur more rapidly.
Original languageEnglish
Pages (from-to)217-227
Number of pages10
JournalJournal of Physiology
Issue number1
Publication statusPublished - 1 Apr 2001


  • frog neuromuscular junction
  • transversus abdominis muscle
  • quantal transmitter release
  • cerebellar granule cells
  • adrenal chromaffin cells
  • garter snake
  • glutamate excitotoxicity
  • synaptic vesicles

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