Interactions of mitochondrial inhibitors with methylmercury on spontaneous quantal release of acetylcholine

Toxicology and Applied Pharmacology
P C Levesque, W D Atchison


The interaction of methylmercury (MeHg) with various inhibitors of mitochondrial function (dinitrophenol, 50 microM; dicoumarol, 100 microM; valinomycin, 20 microM; and ruthenium red, 20 microM) on spontaneous quantal release of acetylcholine was tested at the neuromuscular junction of the rat. The objective was to determine whether these mitochondrial inhibitors blocked the MeHg-induced increase of spontaneous release of acetylcholine, an effect measured electrophysiologically as increased miniature endplate potential (MEPP) frequency. MEPPs were recorded from myofibers of the rat hemidiaphragm using conventional, intracellular microelectrode recording techniques. When given alone, all four inhibitors increased MEPP frequency from resting levels of 1-2/sec (Hz) to approximately 10-60 Hz after a latency which ranged from 5 to 30 min. MEPP frequency subsequently returned to control levels. Subsequent concomitant application of MeHg (100 microM) with dinitrophenol, dicoumarol, or valinomycin increased MEPP frequency sharply to peak values of 40-60 Hz after 15-20 min. MEPP frequency subsided to pre-MeHg levels 10 min later. The time course and peak MEPP frequency elicited by MeHg after pretreatment with these uncouplers were simil...Continue Reading


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