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首页> 外文期刊>Journal of Computational Neuroscience >Mitochondrial dysfunction and role in spreading depolarization and seizure
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Mitochondrial dysfunction and role in spreading depolarization and seizure

机译:线粒体功能障碍及其在去极化和癫痫发作中的作用

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The effect of pathological phenomena such as epileptic seizures and spreading depolarization (SD) on mitochondria and the potential feedback of mitochondrial dysfunction into the dynamics of those phenomena are complex and difficult to study experimentally due to the simultaneous changes in many variables governing neuronal behavior. By combining a model that accounts for a wide range of neuronal behaviors including seizures, normoxic SD, and hypoxic SD (HSD), together with a detailed model of mitochondrial function and intracellular Ca2+ dynamics, we investigate mitochondrial dysfunction and its potential role in recovery of the neuron from seizures, HSD, and SD. Our results demonstrate that HSD leads to the collapse of mitochondrial membrane potential and cellular ATP levels that recover only when normal oxygen supply is restored. Mitochondrial organic phosphate and pH gradients determine the strength of the depolarization block during HSD and SD, how quickly the cell enters the depolarization block when the oxygen supply is disrupted or potassium in the bath solution is raised beyond the physiological value, and how fast the cell recovers from SD and HSD when normal potassium concentration and oxygen supply are restored. Although not as dramatic as phosphate and pH gradients, mitochondrial Ca2+ uptake has a similar effect on neuronal behavior during these conditions.
机译:诸如癫痫性癫痫发作和传播去极化(SD)的病理现象对线粒体的影响以及线粒体功能障碍对这些现象动力学的潜在反馈是复杂的,并且由于控制神经元行为的许多变量同时发生变化,因此很难通过实验研究。通过结合解释广泛的神经元行为(包括癫痫发作,常氧性SD和低氧性SD(HSD))的模型以及线粒体功能和细胞内Ca2 +动力学的详细模型,我们研究了线粒体功能障碍及其在恢复线粒体中的潜在作用。癫痫发作,HSD和SD中的神经元。我们的结果表明,HSD导致线粒体膜电位和细胞ATP水平崩溃,只有在恢复正常的氧气供应后才能恢复。线粒体有机磷酸盐和pH梯度决定了HSD和SD期间去极化功能块的强度,氧气供应中断或浴液中的钾离子升高至超过生理值时细胞进入去极化功能块的速度以及细胞速度有多快恢复正常的钾浓度和氧气供应后,可从SD和HSD中恢复。尽管不如磷酸盐和pH梯度那么剧烈,但在这些情况下,线粒体Ca 2+的吸收对神经元行为具有相似的影响。

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