Calupca, Michelle A. and Prior, Chris and Merriam, Laura A. and Hendricks, Gregory M. and Parsons, Rodney L. (2001) Presynaptic function is altered in snake K+-depolarized motor nerve terminals containing compromised mitochondria. Journal of Physiology, 532 (1). pp. 217-227. ISSN 0022-3751Full text not available in this repository. (Request a copy from the Strathclyde author)
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.
|Keywords:||frog neuromuscular junction, transversus abdominis muscle, quantal transmitter release, cerebellar granule cells, adrenal chromaffin cells, garter snake, glutamate excitotoxicity, synaptic vesicles, Pharmacy and materia medica, Physiology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Strathprints Administrator|
|Date Deposited:||07 Jul 2010 14:01|
|Last modified:||04 May 2016 16:41|