Inhibition of Qi site of mitochondrial complex III with antimycin A decreases persistent and transient sodium currents via reactive oxygen species and protein kinase C in rat hippocampal CA1 cells

Lai, Bin; Zhang, Li; Dong, Lian-Yan; Zhu, Yanhua; Sun, Feng-Yan; Zheng, Ping

doi:10.1016/j.expneurol.2005.03.005

Cited by 26 publications

(22 citation statements)

References 56 publications

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“…ISO, like the complex III Q i site inhibitor AA [37–39], increased the duration of state 3 ΔΨ m (Fig. 3A,C) implying that ISO may attenuate complex III in addition to complex I.…”

Section: Discussionmentioning

confidence: 99%

Isoflurane modulates cardiac mitochondrial bioenergetics by selectively attenuating respiratory complexes

Agarwal

Dash

Stowe

et al. 2014

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Mitochondrial dysfunction contributes to cardiac ischemia-reperfusion (IR) injury but volatile anesthetics (VA) may alter mitochondrial function to trigger cardioprotection. We hypothesized that the VA isoflurane (ISO) mediates cardioprotection in part by altering the function of several respiratory and transport proteins involved in oxidative phosphorylation (OxPhos). To test this we used fluorescence spectrophotometry to measure the effects of ISO (0, 0.5, 1, 2 mM) on the time-course of interlinked mitochondrial bioenergetic variables during states 2, 3 and 4 respiration in the presence of either complex I substrate K+-pyruvate/malate (PM) or complex II substrate K+-succinate (SUC) at physiological levels of extra-matrix free Ca2+ (~200 nM) and Na+ (10 mM). To mimic ISO effects on mitochondrial functions and to clearly delineate the possible ISO targets, the observed actions of ISO were interpreted by comparing effects of ISO to those elicited by low concentrations of inhibitors that act at each respiratory complex, e.g. rotenone (ROT) at complex I or antimycin A (AA) at complex III. Our conclusions are based primarily on the similar responses of ISO and titrated concentrations of ETC inhibitors during state 3. We found that with the substrate PM, ISO and ROT similarly decreased the magnitude of state 3 NADH oxidation and increased the duration of state 3 NADH oxidation, ΔΨm depolarization, and respiration in a concentration-dependent manner, whereas with substrate SUC, ISO and ROT decreased the duration of state 3 NADH oxidation, ΔΨm depolarization and respiration. Unlike AA, ISO reduced the magnitude of state 3 NADH oxidation with PM or SUC as substrate. With substrate SUC, after complete block of complex I with ROT, ISO and AA similarly increased the duration of state 3 ΔΨm depolarization and respiration. This study provides a mechanistic understanding in how ISO alters mitochondrial function in a way that may lead to cardioprotection.

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“…ISO, like the complex III Q i site inhibitor AA [37–39], increased the duration of state 3 ΔΨ m (Fig. 3A,C) implying that ISO may attenuate complex III in addition to complex I.…”

Section: Discussionmentioning

confidence: 99%

Isoflurane modulates cardiac mitochondrial bioenergetics by selectively attenuating respiratory complexes

Agarwal

Dash

Stowe

et al. 2014

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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“…Current and voltage-clamp recordings in cultured cells were conducted using the whole-cell patch-clamp technique [17,18]. Patch electrodes were constructed from thin-walled, 1.5-mm outside diameter borosilicate glass on a Flaming/Brown P-97 pipette puller (Sutter Instruments, Novato, CA), to a final inside diameter of 1-2 m. The patch electrodes had resistances of 4-5 M⍀ when filled with intracellular solution containing 140 mM K-gluconate, 0.1 mM CaCl 2 , 2 mM MgCl 2 , 1 mM EGTA, 2 mM K 2 ATP, 0.1 mM Na 3 GTP, and 10 mM HEPES (pH adjusted to 7.25 with KOH).…”

Section: Patch-clamp Recordingmentioning

confidence: 99%

Endothelium-Induced Proliferation and Electrophysiological Differentiation of Human Embryonic Stem Cell-Derived Neuronal Precursors

Lai

Greenberg

Jin

2008

Stem Cells and Development

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Neurogenesis occurs in a stem cell niche in which vascular elements, including endothelial cells (ECs), are thought to play an important role. Using co-culture experiments, we investigated the effect of ECs on proliferation and functional neuronal differentiation of human embryonic stem (ES) cellderived neuronal precursor cells (NPCs). NPCs were cultured for 5 days in medium containing fibroblast growth factor-2 (FGF-2), with or without ECs. FGF-2 and ECs were then removed, and NPCs were maintained in culture for additional periods. Compared to control NPC cultures, EC-treated NPC cultures showed increased cell proliferation at short intervals (5 days) after withdrawal of FGF-2 and larger tetrodotoxin-sensitive inward membrane currents at longer intervals (10-14 days), but a similar pattern of development of neuronal differentiation markers. The effects of ECs appeared to result from the release of soluble factors rather than from cell contact, because they were observed despite the physical separation of NPCs from ECs by a cell-impermeable membrane. These findings indicate that ECs can regulate the proliferation and electrophysiological neuronal differentiation of human NPCs.

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“…Antimycin A binds at the Q I sites (internal Q, in proximity to the matrix), and inhibits the electron transfer from semiquinone to Q I (Lai et al, 2005), whereas myxothiazol binds at external Q 0 (in proximity to the intermembrane space). Antimycin A and myxothiazol have both been used to study the catalytic activity and structural characteristics of complex III (Miyoshi, 1998;Rieske et al, 1967).…”

Section: Complex II Inhibitors-mentioning

confidence: 99%

“…To test the effect of complex III inhibition that is observed during hypoxia, antimycin A (3 μM) was applied to acutely dissociated CA1 pyramidal neurons (Lai et al, 2005). Antimycin A decreased Na + currents and subsequently neuronal excitability, possibly through H 2 O 2 production, and increased activity of protein kinase C (PKC).…”

Section: Complex II Inhibitors-mentioning

confidence: 99%

Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

Foster

Galeffi

Gerich

et al. 2006

Progress in Neurobiology

164

135

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Mitochondria are critical for cellular ATP production; however, recent studies suggest that these organelles fulfill a much broader range of tasks. For example, they are involved in the regulation of cytosolic Ca 2+ levels, intracellular pH and apoptosis, and are the major source of reactive oxygen species (ROS). Various reactive molecules that originate from mitochondria, such as ROS, are critical in pathological events, such as ischemia, as well as in physiological events such as long-term potentiation, neuronal-vascular coupling and neuronal-glial interactions. Due to their key roles in the regulation of several cellular functions, the dysfunction of mitochondria may be critical in various brain disorders. There has been increasing interest in the development of tools that modulate mitochondrial function, and the refinement of techniques that allow for real time monitoring of mitochondria, particularly within their intact cellular environment. Innovative imaging techniques are especially powerful since they allow for mitochondrial visualization at high resolution, tracking of mitochondrial structures and optical real time monitoring of parameters of mitochondrial function. Among the techniques discussed are the uses of classic imaging techniques such as rhodamine-123, the highly advanced semi-conductor nanoparticles (quantum dots), and wide field microscopy as well as high-resolution multi-photon imaging. We have highlighted the use of these techniques to study mitochondrial function in brain tissue and have included studies from our laboratories in which these techniques have been successfully applied.

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Inhibition of Qi site of mitochondrial complex III with antimycin A decreases persistent and transient sodium currents via reactive oxygen species and protein kinase C in rat hippocampal CA1 cells

Cited by 26 publications

References 56 publications

Isoflurane modulates cardiac mitochondrial bioenergetics by selectively attenuating respiratory complexes

Isoflurane modulates cardiac mitochondrial bioenergetics by selectively attenuating respiratory complexes

Endothelium-Induced Proliferation and Electrophysiological Differentiation of Human Embryonic Stem Cell-Derived Neuronal Precursors

Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

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