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• W2028167712 startingPage "10029" @default.
• W2028167712 abstract "Mitochondrial dysfunction is a potential causal factor in Parkinson's disease. We show here that acute exposure to the mitochondrial complex I inhibitor rotenone (30-100 n m ; 30 min) causes concentration-dependent suppression of single-pulse evoked dopamine (DA) release monitored in real time with carbon-fiber microelectrodes in guinea pig striatal slices, with no effect on DA content. Suppression of DA release was prevented by the sulfonylurea glibenclamide, implicating ATP-sensitive K + (K ATP ) channels; however, tissue ATP was unaltered. Because K ATP channels can be activated by hydrogen peroxide (H 2 O 2 ), as well as by low ATP, we examined the involvement of rotenone-enhanced H 2 O 2 generation. Confirming an essential role for H 2 O 2 , the inhibition of DA release by rotenone was prevented by catalase, a peroxide-scavenging enzyme. Striatal H 2 O 2 generation during rotenone exposure was examined in individual medium spiny neurons using fluorescence imaging with dichlorofluorescein (DCF). An increase in intracellular H 2 O 2 levels followed a similar time course to that of DA release suppression and was accompanied by cell membrane depolarization, decreased input resistance, and increased excitability. Extracellular catalase markedly attenuated the increase in DCF fluorescence and prevented rotenone-induced effects on membrane properties; membrane changes were also largely prevented by flufenamic acid, a blocker of transient receptor potential (TRP) channels. Thus, partial mitochondrial inhibition can cause functional DA denervation via H 2 O 2 and K ATP channels, without DA or ATP depletion. Furthermore, amplified H 2 O 2 levels and TRP channel activation in striatal spiny neurons indicate potential sources of damage in these cells. Overall, these novel factors could contribute to parkinsonian motor deficits and neuronal degeneration caused by mitochondrial dysfunction." @default.
• W2028167712 created "2016-06-24" @default.
• W2028167712 creator A5043025373 @default.
• W2028167712 creator A5057603195 @default.
• W2028167712 creator A5076362309 @default.
• W2028167712 date "2005-10-26" @default.
• W2028167712 modified "2023-09-29" @default.
• W2028167712 title "Partial Mitochondrial Inhibition Causes Striatal Dopamine Release Suppression and Medium Spiny Neuron Depolarization via H₂O₂Elevation, Not ATP Depletion" @default.
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• W2028167712 doi "https://doi.org/10.1523/jneurosci.2652-05.2005" @default.
• W2028167712 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6725568" @default.
• W2028167712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16251452" @default.
• W2028167712 hasPublicationYear "2005" @default.
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