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

• Published in: The Journal of physiology 2001-04, Vol.532 (1), p.217-227
• Main Authors: Calupca, Michelle A, Prior, Chris, Merriam, Laura A, Hendricks, Gregory M, Parsons, Rodney L
• Format: Article
• Language: English
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2001.0217g.x

* 1 Presynaptic function was investigated at K super(+)-stimulated motor nerve terminals in snake costocutaneous nerve muscle preparations exposed to carbonyl cyanide m-chlorophenylhydrazone (CCCP, 2 mu m), oligomycin (8 mu g ml super(-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 super(+) (35 mm), MEPC frequencies initially increased to values > 350 s super(-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 super(+) stimulation, respectively. * 4 The addition of glucose to stimulate production of ATP by glycolysis during sustained K super(+) 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 super(+)-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 super(2+)] sub(i)). For oligomycin-treated nerve terminals, a progressive elevation of [Ca super(2+)] sub(i) could occur as the cytoplasmic ATP/ADP ratio decreases, causing energy-dependent Ca super(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 super(2+) buffering and ATP production were both inhibited. Therefore, the proposed sustained elevation of [Ca super(2+)] sub(i) could occur more rapidly.