The role of extracellular potassium dynamics in the different stages of ictal bursting and spreading depression: A computational study
The role of extracellular potassium dynamics in the different stages of ictal bursting and spreading depression: A computational study
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DOI：
10.1016/j.jtbi.2009.01.032
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发表时间：
2009-05-21
影响因子：
2
通讯作者：
Kurths, Juergen
中科院分区：
文献类型：
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作者：
Florence, Gerson;Dahlem, Markus A.;Kurths, Juergen
实验证据表明，非突触机制（如细胞外吨的波动）参与了癫痫样爆发和扩张性抑制（SD）。在这些异常振荡模式中，观察到细胞外钾浓度[K+](o)的增加和细胞外钙浓度[Ca2+](o)的减少，从而提高神经元的兴奋性。然而，高[K+](o)是触发和传播这些异常神经元活动还是在这一过程中起次要作用尚不清楚。为了更好地理解这些振荡模式下细胞外钾动力学的影响，我们在扩展的Golomb模型中复制了高[K+](o)和零[Ca2+](o)的实验条件，并添加了离子浓度的重要调节机制，如Na+-K+泵、离子扩散和胶质缓冲。在这些条件下，模拟的细胞模型表现出癫痫样放电（垂直爆裂）。SD是由Na+-K+泵活性的中断引起的，模拟细胞缺氧的影响（一种引起SD的实验方案，即缺氧诱导的SD）。采用分岔理论和快慢方法分析了K+动力学对细胞兴奋性的干扰。这一分析表明，系统在高[K+](o)时失去稳定性，过渡到神经元兴奋性升高的状态。高[K+](o)的影响在破裂和破裂的不同阶段被观察到。在初始阶段，[K+](o)的增加为触发两种振荡模式创造了有利条件。在神经元活动期间，向外的K+流使[K+](o)持续增长，以正反馈的方式抑制K+电流。在最后阶段，由于K+电流的抑制，Na+-K+泵是神经元活动结束的主要机制。因此，这项工作表明[K+](o)动力学可能在这些异常振荡模式中起着根本作用。2009爱思唯尔有限公司版权所有。
Experimental evidences point Out the participation of nonsynaptic mechanisms (e.g., fluctuations in extracellular tons) in epileptiform bursting and spreading depression (SD). During these abnormal oscillatory patterns, it is observed an increase of extracellular potassium concentration [K+](o) and a decrease of extracellular calcium concentration [Ca2+](o) which raises the neuronal excitability. However, whether the high [K+](o) triggers and propagates these abnormal neuronal activities or plays a secondary role into this process is unclear. To better understand the influence of extracellular potassium dynamics in these oscillatory patterns, the experimental conditions of high [K+](o) and zero [Ca2+](o) were replicated in an extended Golomb model where we added important regulatory mechanisms of ion concentration as Na+-K+ pump, ion diffusion and glial buffering. Within these Conditions, simulations of the cell model exhibit seizure-like discharges (ictal bursting). The SD was elicited by the interruption of the Na+-K+ pump activity, mimicking the effect of cellular hypoxia (an experimental protocol to elicit SD, the hypoxia-induced SD). We used the bifurcation theory and the fast-slow method to analyze the interference of K+ dynamics in the cellular excitability. This analysis indicates that the system loses its stability at a high [K+](o), transiting to an elevated state of neuronal excitability. Effects of high [K+](o), are observed in different stages of ictal bursting and SD. In the initial stage, the increase of [K+](o) creates favorable conditions to trigger both oscillatory patterns. During the neuronal activity, a continuous growth of [K+](o) by outward K+ flow depresses K+ Currents in a positive feedback way. At the last stage, due to the depression of K+ currents, the Na+-K+ pump is the main mechanism in the end of neuronal activity. Thus, this work suggests that [K+](o) dynamics may play a fundamental role in these abnormal oscillatory patterns. (C) 2009 Elsevier Ltd. All rights reserved.