Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diamide, which in concentrations of 10(-5) M and higher oxidizes glutathione intracellularly, produces a dose-related increase in the frequency of miniature end-plate potentials (MEPPs). With high enough doses, quantal release is blocked, apparently through exhaustion. The early phase of MEPP frequency increase is accompanied by an increase in EPP amplitude that may reach more than 10-fold and is therefore not produced by depolarization of axon terminals. Subsequently, EPP amplitude is reduced and falls to zero, associated with failure of invasion of the nerve action into the terminals while the MEPP frequency remains elevated. Both facilitation and PTP follow the time course of change in EPP amplitude. The increase in MEPP frequency with diamide does not require external Ca2+ but raising external Ca2+ increases the MEPP rate in the presence of diamide. External Ca2+ is necessary for EPP appearance and also potentiates the diamide effects. Conversely diamide reduces the requirements for Ca2+ in releasing ACh. Diamide substitutes for external Ca2+ in K+ evoked MEPP release and in the absence of external Ca2+, diamide-evoked MEPP release is increased by raising external Mg2+ levels. The action of diamide may be dependent on the actual release of Ca2+ from intracellular stores or it may work through mimicking some of the actions of Ca2+. The action of diamide bears close resemblance to the effects of prolonged stimulation of the motor axon at 10 Hz.
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PMID:The thiol-oxidizing agent diamide increases transmitter release by decreasing calcium requirements for neuromuscular transmission in the frog. 18 54

The thiol-oxidizing agent diamide markedly increases m.e.p.p. frequency at the frog neuromuscular junction, even at low [Ca2+]0 and also when the mitochondria are uncoupled with DNP. The effect is reversed by dithioerythritol and is very temperature-sensitive, with a marked transition at 16 degrees C; m.e.p.p. frequency is raised 2- to 5-fold at 13-15 degrees C and 55- to 60-fold at 17-20 degrees C. Diamide increases the frequency of large amplitude m.e.p.p.s, the effect being explicable as the fusion of two or more vesicles. It is concluded that (a) diamide does not act at the Ca2+ channels of the plasma membrane, nor at the mitochondria. It affects the release system directly via an alteration of membrane protein --SH groups; (b) the eventual decline in m.e.p.p. frequency after DNP treatment is because of the exhaustion of mitochondrial Ca2+ rather than a depletion of quanta; (c) the major effect of temperature is on the release mechanism, perhaps via a phase-change in the phospholipoproteins of the plasmalemma or vesicles, rather than an elevation of [Ca2+]i; (d) either diamide or temperatures above 16 degrees C make Ca2+ more effective in promoting vesicle-plasmalemma fusion.
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PMID:Diamide, temperature and spontaneous transmitter release at the neuromuscular junction: stimulation of exocytosis by a direct effect on membrane fusion? 611 68