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Mitochondrial uncoupling by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP, 1 \u03bcM) prior to hypoxia hastened the onset and shortened the duration of HSD. Blocking mitochondrial ATP synthesis by oligomycin (10 \u03bcg\/ml) was without effect. Inhibition of mitochondrial respiration by rotenone (20 \u03bcM), diphenyleneiodonium (25 \u03bcM), or antimycin A (20 \u03bcM) also hastened HSD onset and shortened HSD duration. 3-nitropropionic acid (1 mM) increased HSD duration. Cyanide (100 \u03bcM) hastened HSD onset and increased HSD duration. At higher concentrations, cyanide (1 mM), azide (2 mM), and FCCP (10 \u03bcM) triggered SD episodes on their own. Compared with control HSD, the spatial extent of the intrinsic optical signals of cyanide- and azide-induced SDs was more pronounced. Monitoring NADH (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) autofluorescence and mitochondrial membrane potential verified the mitochondrial targeting by the drugs used. Except 1 mM cyanide, no treatment reduced cellular ATP levels severely and no correlation was found between ATP, NADH, or FAD levels and the time to HSD onset. Therefore ATP depletion or a cytosolic reducing shift due to NADH\/FADH<jats:sub>2<\/jats:sub>accumulation cannot serve as a general explanation for the hastening of HSD onset on mitochondrial inhibition. Additional redox couples (glutathione) or events downstream of the mitochondrial depolarization need to be considered.<\/jats:p>","DOI":"10.1152\/jn.01015.2005","type":"journal-article","created":{"date-parts":[[2006,4,13]],"date-time":"2006-04-13T00:45:36Z","timestamp":1144889136000},"page":"492-504","source":"Crossref","is-referenced-by-count":49,"title":["Mitochondrial Inhibition Prior to Oxygen-Withdrawal Facilitates the Occurrence of Hypoxia-Induced Spreading Depression in Rat Hippocampal Slices"],"prefix":"10.1152","volume":"96","author":[{"given":"Florian J.","family":"Gerich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Hepp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irmelin","family":"Probst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1999.0762"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.80.3.1514"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4157-04.2005"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1999.0771"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.84.1.311"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01674-1"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-18-07189.1998"},{"key":"R8","unstructured":"Berg JM, Tymoczko JL, and Stryer L.Biochemistry.New York: Freeman, 2002."},{"key":"R9","unstructured":"Bindokas VP, Jordan J, Lee CC, and Miller RJ.Superoxide production in rat hippocampal neurons: selective imaging with hydroethidine.J Neurosci15: 1324\u20131336, 1996."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1042\/bj1340707"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04203.x"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Chance Band Williams GR.Respiratory enzymes in oxidative phosphorylation. 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