The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
Ellen F. Barett - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial Ca2+ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals
Journal of Physiology, 2003Co-Authors: Gavriel David, Ellen F. BarettAbstract:We investigated how inhibition of mitochondrial Ca2+ uptake affects transmitter release from mouse motor terminals during brief trains of action potentials (500 at 50 Hz) in physiological bath [Ca2+]. When mitochondrial Ca2+ uptake was inhibited by depolarizing mitochondria with Antimycin A1 or carbonyl cyanide m-chlorophenyl-hydrazone, the stimulation-induced increase in cytosolic [Ca2+] was greater (> 10 microM, compared to < or = 1 microM in control solution), the quantal content of the endplate potential (EPP) depressed more rapidly (approximately 84 % depression compared to approximately 8 % in controls), and asynchronous release during the stimulus train reached higher frequencies (peak rates of approximately 6000 s-1 compared to approximately 75 s-1 in controls). These effects of mitochondrial depolarization were not accompanied by a significant change in EPP quantal content or the rate of asynchronous release during 1 Hz stimulation, and were not seen in oligomycin, which blocks mitochondrial ATP synthesis without depolarizing mitochondria. Inhibition of endoplasmic reticular Ca2+ uptake with cyclopiazonic acid also had little effect on stimulation-induced changes in cytosolic [Ca2+] or EPP amplitude. We hypothesize that the high rate of asynchronous release evoked by stimulation during mitochondrial depolarization was produced by the elevation of cytosolic [Ca2+], and contributed to the accelerated depression of phasic release by reducing the availability of releasable vesicles. During mitochondrial depolarization, the post-tetanic potentiation of the EPP observed under control conditions was replaced by a post-tetanic depression with a slow time course of recovery. Thus, mitochondrial Ca2+ uptake is essential for sustaining phasic release, and thus neuromuscular transmission, during and following tetanic stimulation.
Gavriel David - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial Ca2+ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals
Journal of Physiology, 2003Co-Authors: Gavriel David, Ellen F. BarettAbstract:We investigated how inhibition of mitochondrial Ca2+ uptake affects transmitter release from mouse motor terminals during brief trains of action potentials (500 at 50 Hz) in physiological bath [Ca2+]. When mitochondrial Ca2+ uptake was inhibited by depolarizing mitochondria with Antimycin A1 or carbonyl cyanide m-chlorophenyl-hydrazone, the stimulation-induced increase in cytosolic [Ca2+] was greater (> 10 microM, compared to < or = 1 microM in control solution), the quantal content of the endplate potential (EPP) depressed more rapidly (approximately 84 % depression compared to approximately 8 % in controls), and asynchronous release during the stimulus train reached higher frequencies (peak rates of approximately 6000 s-1 compared to approximately 75 s-1 in controls). These effects of mitochondrial depolarization were not accompanied by a significant change in EPP quantal content or the rate of asynchronous release during 1 Hz stimulation, and were not seen in oligomycin, which blocks mitochondrial ATP synthesis without depolarizing mitochondria. Inhibition of endoplasmic reticular Ca2+ uptake with cyclopiazonic acid also had little effect on stimulation-induced changes in cytosolic [Ca2+] or EPP amplitude. We hypothesize that the high rate of asynchronous release evoked by stimulation during mitochondrial depolarization was produced by the elevation of cytosolic [Ca2+], and contributed to the accelerated depression of phasic release by reducing the availability of releasable vesicles. During mitochondrial depolarization, the post-tetanic potentiation of the EPP observed under control conditions was replaced by a post-tetanic depression with a slow time course of recovery. Thus, mitochondrial Ca2+ uptake is essential for sustaining phasic release, and thus neuromuscular transmission, during and following tetanic stimulation.
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Stimulation-Evoked Increases in Cytosolic [Ca2+] in Mouse Motor Nerve Terminals Are Limited by Mitochondrial Uptake and Are Temperature-Dependent
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000Co-Authors: Gavriel David, Ellen F. BarrettAbstract:Increases in cytosolic [Ca(2+)] evoked by trains of action potentials (20-100 Hz) were recorded from mouse and lizard motor nerve terminals filled with a low-affinity fluorescent indicator, Oregon Green BAPTA 5N. In mouse terminals at near-physiological temperatures (30-38 degrees C), trains of action potentials at 25-100 Hz elicited increases in cytosolic [Ca(2+)] that stabilized at plateau levels that increased with stimulation frequency. Depolarization of mitochondria with carbonylcyanide m-chlorophenylhydrazone (CCCP) or Antimycin A1 caused cytosolic [Ca(2+)] to rise to much higher levels during stimulation. Thus, mitochondrial Ca(2+) uptake contributes importantly to limiting the rise of cytosolic [Ca(2+)] during repetitive stimulation. In mouse terminals, the stimulation-induced increase in cytosolic [Ca(2+)] was highly temperature-dependent over the range 18-38 degrees C, with greater increases at lower temperatures. At the lower temperatures, application of CCCP continued to depolarize mitochondria but produced a much smaller increase in the cytosolic [Ca(2+)] transient evoked by repetitive stimulation. This result suggests that the larger amplitude of the stimulation-induced cytosolic [Ca(2+)] transient at lower temperatures was attributable in part to reduced mitochondrial Ca(2+) uptake. In contrast, the stimulation-induced increases in cytosolic [Ca(2+)] measured in lizard motor terminals showed little or no temperature-dependence over the range 18-33 degrees C.
Jurgen Kopitz - One of the best experts on this subject based on the ideXlab platform.
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ginkgo extract egb 761 shields from slowly accumulating neurodegenerative like changes in a newly developed cell culture model induced by the combined action of low doses of Antimycin A1 and 2 deoxy d glucose
Journal of Neural Transmission, 2011Co-Authors: Konstanze Plaschke, Marion Bergmann, Jurgen KopitzAbstract:Different cell culture models were already used to analyze the molecular base of the neuroprotective activities of the Ginkgo biloba extract EGb 761(®) after a single or short-term application. In these previous studies cells were severely injured with agents that promptly induce fatal cellular damage, like vast oxidative stress or mitochondrial dysfunction, and the protective effects of EGb 761(®) on such acute damage were evaluated. Our present study aimed to test EGb 761(®) action in cell cultures, where cellular functions are only moderately impaired by a longer lasting, but relatively modest oxidative stress, reduction of mitochondrial function and reduced intracellular energy levels, thereby causing only slow occurence of cellular damage over a time period of 2 weeks. To this end we used neuroblastoma cells (SK-N-MC) that were treated with low doses of a combination of Antimycin A1 and 2-deoxy-D: -glucose. Addition of EGb 761(®) to the culture medium efficiently shielded the cells from progressing injury by reduced ATP-levels, oxidized redox state, lipid peroxidation damage and oxidative damage of mitochondrial DNA. As a result the cells were protected from apoptotic death that was observed in cultures without EGb 761(®) after 2 weeks of damage occurence. This cell culture system characterizing moderate cellular stress will be applied in future studies to further investigate the mode of action of single EGb 761(®) compounds.
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Ginkgo extract EGb 761^® shields from slowly accumulating neurodegenerative-like changes in a newly developed cell culture model induced by the combined action of low doses of Antimycin A1 and 2-deoxy-d-glucose
Journal of Neural Transmission, 2011Co-Authors: Konstanze Plaschke, Marion Bergmann, Jurgen KopitzAbstract:Different cell culture models were already used to analyze the molecular base of the neuroprotective activities of the Ginkgo biloba extract EGb 761^® after a single or short-term application. In these previous studies cells were severely injured with agents that promptly induce fatal cellular damage, like vast oxidative stress or mitochondrial dysfunction, and the protective effects of EGb 761^® on such acute damage were evaluated. Our present study aimed to test EGb 761^® action in cell cultures, where cellular functions are only moderately impaired by a longer lasting, but relatively modest oxidative stress, reduction of mitochondrial function and reduced intracellular energy levels, thereby causing only slow occurence of cellular damage over a time period of 2 weeks. To this end we used neuroblastoma cells (SK-N-MC) that were treated with low doses of a combination of Antimycin A1 and 2-deoxy- d -glucose. Addition of EGb 761^® to the culture medium efficiently shielded the cells from progressing injury by reduced ATP-levels, oxidized redox state, lipid peroxidation damage and oxidative damage of mitochondrial DNA. As a result the cells were protected from apoptotic death that was observed in cultures without EGb 761^® after 2 weeks of damage occurence. This cell culture system characterizing moderate cellular stress will be applied in future studies to further investigate the mode of action of single EGb 761^® compounds.
Gregory A. Lnenicka - One of the best experts on this subject based on the ideXlab platform.
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Ca2+ clearance at growth cones produced by crayfish motor axons in an explant culture.
Journal of neurophysiology, 2003Co-Authors: Nidhi Rumpal, Gregory A. LnenickaAbstract:Intracellular free Ca2+ concentration ([Ca2+]i) plays an important role in the regulation of growth cone (GC) motility; however, the mechanisms responsible for clearing Ca2+ from GCs have not been examined. We studied the Ca2+-clearance mechanisms in GCs produced by crayfish tonic and phasic motor axons by measuring the decay of [Ca2+]i after a high [K+] depolarizing pulse using fura-2AM. Tonic motor axons regenerating in explant cultures develop GCs with more rapid Ca2+ clearance than GCs from phasic axons. When Na/Ca exchange was blocked by replacing external Na+ with N-methyl-d-glucamine (NMG), [Ca2+]i decay was delayed in both tonic and phasic GCs. Tonic GCs appear to have higher Na/Ca exchange activity than phasic ones since reversal of Na/Ca exchange by lowering external Na+ caused a greater increase in [Ca2+]i for tonic than phasic GCs. Application of the mitochondrial inhibitors, Antimycin A1 (1 μM) and CCCP (10 μM), demonstrated that mitochondrial Ca2+ uptake/release was more prominent in phasic ...
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Ca2+ Clearance at Growth Cones Produced by Crayfish Motor Axons in an Explant Culture
Journal of Neurophysiology, 2003Co-Authors: Nidhi Rumpal, Gregory A. LnenickaAbstract:Intracellular free Ca2+ concentration ([Ca2+]i) plays an important role in the regulation of growth cone (GC) motility; however, the mechanisms responsible for clearing Ca2+ from GCs have not been examined. We studied the Ca2+-clearance mechanisms in GCs produced by crayfish tonic and phasic motor axons by measuring the decay of [Ca2+]i after a high [K+] depolarizing pulse using fura-2AM. Tonic motor axons regenerating in explant cultures develop GCs with more rapid Ca2+ clearance than GCs from phasic axons. When Na/Ca exchange was blocked by replacing external Na+ with N-methyl-d-glucamine (NMG), [Ca2+]i decay was delayed in both tonic and phasic GCs. Tonic GCs appear to have higher Na/Ca exchange activity than phasic ones since reversal of Na/Ca exchange by lowering external Na+ caused a greater increase in [Ca2+]i for tonic than phasic GCs. Application of the mitochondrial inhibitors, Antimycin A1 (1 μM) and CCCP (10 μM), demonstrated that mitochondrial Ca2+ uptake/release was more prominent in phasic than tonic GCs. When both Na/Ca exchange and mitochondria were inhibited, the plasma membrane Ca2+ ATPase was effective in extruding Ca2+ from tonic, but not phasic GCs. We conclude that Na/Ca exchange plays a prominent role in extruding large Ca2+ loads from both tonic and phasic GCs. High Na/Ca exchange activity in tonic GCs contributes to the rapid decay of [Ca2+]i in these GCs; low rates of Ca2+ extrusion plus the release of Ca2+ from mitochondria prolongs the decay of [Ca2+]i in the phasic GCs.
Konstanze Plaschke - One of the best experts on this subject based on the ideXlab platform.
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ginkgo extract egb 761 shields from slowly accumulating neurodegenerative like changes in a newly developed cell culture model induced by the combined action of low doses of Antimycin A1 and 2 deoxy d glucose
Journal of Neural Transmission, 2011Co-Authors: Konstanze Plaschke, Marion Bergmann, Jurgen KopitzAbstract:Different cell culture models were already used to analyze the molecular base of the neuroprotective activities of the Ginkgo biloba extract EGb 761(®) after a single or short-term application. In these previous studies cells were severely injured with agents that promptly induce fatal cellular damage, like vast oxidative stress or mitochondrial dysfunction, and the protective effects of EGb 761(®) on such acute damage were evaluated. Our present study aimed to test EGb 761(®) action in cell cultures, where cellular functions are only moderately impaired by a longer lasting, but relatively modest oxidative stress, reduction of mitochondrial function and reduced intracellular energy levels, thereby causing only slow occurence of cellular damage over a time period of 2 weeks. To this end we used neuroblastoma cells (SK-N-MC) that were treated with low doses of a combination of Antimycin A1 and 2-deoxy-D: -glucose. Addition of EGb 761(®) to the culture medium efficiently shielded the cells from progressing injury by reduced ATP-levels, oxidized redox state, lipid peroxidation damage and oxidative damage of mitochondrial DNA. As a result the cells were protected from apoptotic death that was observed in cultures without EGb 761(®) after 2 weeks of damage occurence. This cell culture system characterizing moderate cellular stress will be applied in future studies to further investigate the mode of action of single EGb 761(®) compounds.
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Ginkgo extract EGb 761^® shields from slowly accumulating neurodegenerative-like changes in a newly developed cell culture model induced by the combined action of low doses of Antimycin A1 and 2-deoxy-d-glucose
Journal of Neural Transmission, 2011Co-Authors: Konstanze Plaschke, Marion Bergmann, Jurgen KopitzAbstract:Different cell culture models were already used to analyze the molecular base of the neuroprotective activities of the Ginkgo biloba extract EGb 761^® after a single or short-term application. In these previous studies cells were severely injured with agents that promptly induce fatal cellular damage, like vast oxidative stress or mitochondrial dysfunction, and the protective effects of EGb 761^® on such acute damage were evaluated. Our present study aimed to test EGb 761^® action in cell cultures, where cellular functions are only moderately impaired by a longer lasting, but relatively modest oxidative stress, reduction of mitochondrial function and reduced intracellular energy levels, thereby causing only slow occurence of cellular damage over a time period of 2 weeks. To this end we used neuroblastoma cells (SK-N-MC) that were treated with low doses of a combination of Antimycin A1 and 2-deoxy- d -glucose. Addition of EGb 761^® to the culture medium efficiently shielded the cells from progressing injury by reduced ATP-levels, oxidized redox state, lipid peroxidation damage and oxidative damage of mitochondrial DNA. As a result the cells were protected from apoptotic death that was observed in cultures without EGb 761^® after 2 weeks of damage occurence. This cell culture system characterizing moderate cellular stress will be applied in future studies to further investigate the mode of action of single EGb 761^® compounds.