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Presynaptic function is altered in snake K + ‐depolarized motor nerve terminals containing compromised mitochondria
Author(s) -
Calupca Michelle A.,
Prior Chris,
Merriam Laura A.,
Hendricks Gregory M.,
Parsons Rodney L.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0217g.x
Subject(s) - oligomycin , biophysics , stimulation , synaptic vesicle , glycolysis , chemistry , membrane potential , biochemistry , biology , endocrinology , atpase , vesicle , membrane , metabolism , enzyme
1 Presynaptic function was investigated at K + ‐stimulated motor nerve terminals in snake costocutaneous nerve muscle preparations exposed to carbonyl cyanide m ‐chlorophenylhydrazone (CCCP, 2 μ m ), oligomycin (8 μg ml −1 ) or CCCP and oligomycin together. 2 Miniature endplate currents (MEPCs) were recorded at ‐150 mV with two‐electrode voltage clamp. With all three drug treatments, during stimulation by elevated K + (35 m m ), MEPC frequencies initially increased to values > 350 s −1 , but then declined. The decline occurred more rapidly in preparations treated with CCCP or CCCP and oligomycin together than in those treated with oligomycin alone. 3 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. 4 The addition of glucose to stimulate production of ATP by 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. 5 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 ([Ca 2+ ] i ). For oligomycin‐treated nerve terminals, a progressive elevation of [Ca 2+ ] i could occur as the cytoplasmic ATP/ADP ratio decreases, causing energy‐dependent Ca 2+ 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 Ca 2+ buffering and ATP production were both inhibited. Therefore, the proposed sustained elevation of [Ca 2+ ] i could occur more rapidly.