MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks

Yan-fang RUI; Zhao-hui SUN; Jia-ping GU; Zhong-hua SHENG; Xiang-ping HE; Zuo-ping XIE

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MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks

机译：MEK抑制剂PD98059急性抑制培养的海马网络中同步的自发Ca2 +振荡

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Aim: To investigate the changes in synchronized spontaneous Ca2+ oscillations induced by mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 at different concentrations in cultured hippocampal network. Methods: Hippocampal neurons in culture for 1-2 weeks were used for this study. Spontaneous synaptic activities of these hippocampal neurons were examined by Ca2+ imaging using calcium-sensitive dye. MEK inhibitor PD98059 (10,30, and 60 μmol/L) and SB202474 (10 and 60 μmol/L), a negative control for mitogen-activated protein kinase (MAPK) cascade study, were applied to the cells under the microscope while imaging was taking place. Results: PD98059 at a lower concentration of 10 μmol/L had little effect on the Ca2+ oscillation. At the higher concentration of 30 μmol/L, 5 min after application of PD98059, the spike frequency was decreased to 25.38%±7.40% (mean±SEM, n=16, F＜0.01 vs medium control) of that of the control period. At an even higher concentration of 60 μmol/L, 5 min after application of PD98059, the spike frequency was decreased to 14.53%±5.34% (mean±SEM, n=16, P＜0.01 vs medium control) of that of the control period. The spike amplitude underwent a corresponding decrease. However, the negative control SB202474 at concentrations of 10 and 60 μmol/L had little inhibition effect on the Ca2+ oscillation. Conclusion: These results indicate that PD98059 inhibits synchronized spontaneous Ca2+ oscillation through inhibition of MEK, which hints that the MAPK cascade is required to maintain synchronized spontaneous Ca2+ oscillation.

机译：目的：探讨培养的海马网络中不同浓度的丝裂剂激活蛋白激酶激酶（MEK）抑制剂PD98059诱导的同步自发CA2 +振荡的变化。方法：本研究使用培养中的海马神经元1-2周。通过Ca2 +成像使用钙敏感染料检查这些海马神经元的自发突触活动。 MEK抑制剂PD98059（10,30和60μmol/ L）和SB202474（10和60μmol/ L），对显微镜下的细胞施加对丝裂剂活化蛋白激酶（MAPK）级联研究的阴性对照，同时成像正在发生。结果：较低浓度为10μmol/ L的PD98059对CA2 +振荡几乎没有影响。在施用PD98059之后，5分钟的较高浓度为30μmol/ L，尖峰频率降至控制期间的25.38％±7.40％（平均±SEM，N = 16，F <0.01 VS中等控制）。在施用PD98059之后，甚至更高浓度的60μmol/ L，5分钟，尖峰频率降低至控制器的14.53％±5.34％（平均±SEM，N = 16，P <0.01 VS中控制）时期。尖峰幅度接受了相应的减少。然而，浓度为10和60μmol/ L的阴性对照SB202474对Ca2 +振荡具有很小的抑制作用。结论：这些结果表明，PD98059通过抑制MEK抑制了同步的自发CA2 +振荡，这提示MAPK级联需要维持同步自发CA2 +振荡。

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《中国药理学报：英文版》 |2006年第7期|869-876|共8页
作者
Yan-fang RUI; Zhao-hui SUN; Jia-ping GU; Zhong-hua SHENG; Xiang-ping HE; Zuo-ping XIE;
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作者单位

Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China;

Institute of Neurological Disorders, Life Science and Medical Department, Tsinghua University, Beijing 100084, China;

Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China;

Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China;

Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China;

Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China;

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原文格式 PDF
正文语种 chi
中图分类药学;
关键词
PD98059; MEK; calcium oscillation;

机译：PD98059;MEK;钙振荡;

MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks

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