The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization.
The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization.
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DOI：
10.1371/journal.pcbi.1004414
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发表时间：
2015-08
影响因子：
4.3
通讯作者：
Schiff SJ
中科院分区：
文献类型：
--
作者：
Ullah G;Wei Y;Dahlem MA;Wechselberger M;Schiff SJ
细胞体积变化在大脑的正常和病理活动中普遍存在。然而，我们对细胞体积如何影响神经元动力学知之甚少。我们在这里首次详细研究了细胞体积对神经元动力学的影响。通过将细胞膨胀与动态离子浓度和氧气供应结合到霍奇金-赫胥黎型尖峰动力学中，我们证明了当细胞响应渗透压变化而膨胀和收缩时，癫痫发作和扩散性抑郁状态之间的自发转变。我们使用体积作为顺序参数进一步揭示了实验描述的生理上限的动态定义，该上限将癫痫发作与扩散性抑郁分开，并预测了区分扩散性抑郁与缺氧去极化的第二个上限。我们的模型强调了神经胶质 K 缓冲癫痫发作和扩散抑郁的神经保护作用，并为缺血期间缺氧去极化和相关细胞肿胀提供了新的见解。我们认为，癫痫发作、扩散性抑郁和缺氧去极化的动态过程是沿着神经元膜的连续体进行的，只有考虑到动态离子浓度、氧稳态和响应渗透压的细胞肿胀，才能理解这一连续体。我们的结果证明了针对各种神经元行为的统一框架的可行性，这对于理解和潜在地开发针对这些病理状态的通用干预策略可能具有重要意义。质膜上离子的大规模重排和细胞体积的变化是癫痫、扩散性抑郁和缺血等状态的常见特征。在本文中，我们重点关注音量本身如何影响神经元活动。我们通过利用以前未探索的共同特征，为各种神经元行为构建了一个统一的计算框架。通过在 Hodgkin-Huxley 型框架内结合动态离子浓度和体积、电荷守恒以及细胞的能量需求，我们证明了涵盖广泛神经元行为的综合框架的可行性。我们展示了当细胞响应不同离子重排导致的不同渗透压而膨胀和收缩时，神经元在癫痫发作和扩散性抑郁之间的自发转变。我们的模型密切再现了缺血期间的缺氧去极化和相关的神经元肿胀，并揭示了实验描述的生理上限的动力学定义，该生理上限将癫痫发作与扩散性抑郁以及缺氧去极化的扩散性抑郁区分开来。这项研究开辟了一种研究神经元行为的新方法，其中不同的状态不需要单独处理，而是作为神经元膜电位及其微环境的动态连续体。
Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little of how cell volume affects neuronal dynamics. We here performed the first detailed study of the effects of cell volume on neuronal dynamics. By incorporating cell swelling together with dynamic ion concentrations and oxygen supply into Hodgkin-Huxley type spiking dynamics, we demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. Our use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial K buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia. We argue that the dynamics of seizures, spreading depression, and anoxic depolarization lie along a continuum of the repertoire of the neuron membrane that can be understood only when the dynamic ion concentrations, oxygen homeostasis,and cell swelling in response to osmotic pressure are taken into consideration. Our results demonstrate the feasibility of a unified framework for a wide range of neuronal behaviors that may be of substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states. Massive rearrangement of ions across the plasma membrane and changes in cellular volume are common features of states such as seizures, spreading depression, and ischemia. In this paper, we focus on how volume itself influences neuronal activity. We build a unified computational framework for a wide range of neuronal behaviors by exploiting their previously unexplored common features. By combining the dynamic ion concentrations and volume, conservation of charge, and the energy requirements of the cell within a Hodgkin-Huxley type framework, we demonstrate the feasibility of a comprehensive framework encompassing a wide range of neuronal behaviors. We show the spontaneous transition of a neuron between seizure and spreading depression when the cell swells and contracts in response to varying osmotic pressure as a result of the rearrangement of different ions. Our model closely reproduces anoxic depolarization and relevant neuronal swelling during ischemia and reveals a dynamical definition for the experimentally described physiological ceilings that demarcate seizure from spreading depression and spreading depression from anoxic depolarization. This study opens up a new way of studying neuronal behavior where different states need not be treated separately but rather as a dynamical continuum of the neuronal membrane potential and its microenvironment.