{"title":"Na+/K+-ATP酶通过剪切尖峰起始分叉结构,使 I 类神经元产生确定性爆发。","authors":"Mahraz Behbood, Louisiane Lemaire, Jan-Hendrik Schleimer, Susanne Schreiber","doi":"10.1371/journal.pcbi.1011751","DOIUrl":null,"url":null,"abstract":"<p><p>Slow brain rhythms, for example during slow-wave sleep or pathological conditions like seizures and spreading depolarization, can be accompanied by oscillations in extracellular potassium concentration. Such slow brain rhythms typically have a lower frequency than tonic action-potential firing. They are assumed to arise from network-level mechanisms, involving synaptic interactions and delays, or from intrinsically bursting neurons. Neuronal burst generation is commonly attributed to ion channels with slow kinetics. Here, we explore an alternative mechanism generically available to all neurons with class I excitability. It is based on the interplay of fast-spiking voltage dynamics with a one-dimensional slow dynamics of the extracellular potassium concentration, mediated by the activity of the Na+/K+-ATPase. We use bifurcation analysis of the complete system as well as the slow-fast method to reveal that this coupling suffices to generate a hysteresis loop organized around a bistable region that emerges from a saddle-node loop bifurcation-a common feature of class I excitable neurons. Depending on the strength of the Na+/K+-ATPase, bursts are generated from pump-induced shearing the bifurcation structure, spiking is tonic, or cells are silenced via depolarization block. We suggest that transitions between these dynamics can result from disturbances in extracellular potassium regulation, such as glial malfunction or hypoxia affecting the Na+/K+-ATPase activity. The identified minimal mechanistic model outlining the sodium-potassium pump's generic contribution to burst dynamics can, therefore, contribute to a better mechanistic understanding of pathologies such as epilepsy syndromes and, potentially, inform therapeutic strategies.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Na+/K+-ATPase generically enables deterministic bursting in class I neurons by shearing the spike-onset bifurcation structure.\",\"authors\":\"Mahraz Behbood, Louisiane Lemaire, Jan-Hendrik Schleimer, Susanne Schreiber\",\"doi\":\"10.1371/journal.pcbi.1011751\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Slow brain rhythms, for example during slow-wave sleep or pathological conditions like seizures and spreading depolarization, can be accompanied by oscillations in extracellular potassium concentration. 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Depending on the strength of the Na+/K+-ATPase, bursts are generated from pump-induced shearing the bifurcation structure, spiking is tonic, or cells are silenced via depolarization block. We suggest that transitions between these dynamics can result from disturbances in extracellular potassium regulation, such as glial malfunction or hypoxia affecting the Na+/K+-ATPase activity. The identified minimal mechanistic model outlining the sodium-potassium pump's generic contribution to burst dynamics can, therefore, contribute to a better mechanistic understanding of pathologies such as epilepsy syndromes and, potentially, inform therapeutic strategies.</p>\",\"PeriodicalId\":20241,\"journal\":{\"name\":\"PLoS Computational Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PLoS Computational Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1371/journal.pcbi.1011751\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Computational Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pcbi.1011751","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
摘要
缓慢的大脑节律,例如在慢波睡眠或癫痫发作和扩散性去极化等病理情况下,可能伴随着细胞外钾浓度的振荡。这种大脑慢节律的频率通常低于强直性动作电位发射。它们被认为是由网络层面的机制引起的,涉及突触的相互作用和延迟,或者是由神经元的内在突发性引起的。神经元爆发的产生通常归因于具有缓慢动力学的离子通道。在这里,我们探索了一种通用于所有具有 I 类兴奋性神经元的替代机制。它基于快速尖峰电压动态与细胞外钾浓度一维慢速动态的相互作用,由 Na+/K+-ATP 酶的活性介导。我们利用完整系统的分叉分析以及慢-快方法揭示出,这种耦合足以产生一个围绕双稳态区域的滞后环,该双稳态区域来自于马鞍节点环分叉--这是第一类可兴奋神经元的共同特征。根据 Na+/K+-ATP 酶的强弱,泵诱导的剪切分叉结构会产生脉冲串,尖峰脉冲是强直性的,或者细胞通过去极化阻滞而沉默。我们认为,细胞外钾调节紊乱(如神经胶质功能失调或缺氧影响 Na+/K+-ATP 酶活性)可能导致这些动态之间的转换。因此,概述钠钾泵对猝发动力学的一般贡献的最小机制模型有助于从机制上更好地理解癫痫综合征等病理,并有可能为治疗策略提供依据。
The Na+/K+-ATPase generically enables deterministic bursting in class I neurons by shearing the spike-onset bifurcation structure.
Slow brain rhythms, for example during slow-wave sleep or pathological conditions like seizures and spreading depolarization, can be accompanied by oscillations in extracellular potassium concentration. Such slow brain rhythms typically have a lower frequency than tonic action-potential firing. They are assumed to arise from network-level mechanisms, involving synaptic interactions and delays, or from intrinsically bursting neurons. Neuronal burst generation is commonly attributed to ion channels with slow kinetics. Here, we explore an alternative mechanism generically available to all neurons with class I excitability. It is based on the interplay of fast-spiking voltage dynamics with a one-dimensional slow dynamics of the extracellular potassium concentration, mediated by the activity of the Na+/K+-ATPase. We use bifurcation analysis of the complete system as well as the slow-fast method to reveal that this coupling suffices to generate a hysteresis loop organized around a bistable region that emerges from a saddle-node loop bifurcation-a common feature of class I excitable neurons. Depending on the strength of the Na+/K+-ATPase, bursts are generated from pump-induced shearing the bifurcation structure, spiking is tonic, or cells are silenced via depolarization block. We suggest that transitions between these dynamics can result from disturbances in extracellular potassium regulation, such as glial malfunction or hypoxia affecting the Na+/K+-ATPase activity. The identified minimal mechanistic model outlining the sodium-potassium pump's generic contribution to burst dynamics can, therefore, contribute to a better mechanistic understanding of pathologies such as epilepsy syndromes and, potentially, inform therapeutic strategies.
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