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神经元钙波需要什么?一项数值参数研究。

What Is Required for Neuronal Calcium Waves? A Numerical Parameter Study.

作者信息

Breit Markus, Queisser Gillian

机构信息

G-CSC, Goethe University Frankfurt, Frankfurt am Main, Germany.

Department of Mathematics, Temple University, Philadelphia, USA.

出版信息

J Math Neurosci. 2018 Jul 13;8(1):9. doi: 10.1186/s13408-018-0064-x.

Abstract

Neuronal calcium signals propagating by simple diffusion and reaction with mobile and stationary buffers are limited to cellular microdomains. The distance intracellular calcium signals can travel may be significantly increased by means of calcium-induced calcium release from internal calcium stores, notably the endoplasmic reticulum. The organelle, which can be thought of as a cell-within-a-cell, is able to sequester large amounts of cytosolic calcium ions via SERCA pumps and selectively release them into the cytosol through ryanodine receptor channels leading to the formation of calcium waves. In this study, we set out to investigate the basic properties of such dendritic calcium waves and how they depend on the three parameters dendrite radius, ER radius and ryanodine receptor density in the endoplasmic membrane. We demonstrate that there are stable and abortive regimes for calcium waves, depending on the above morphological and physiological parameters. In stable regimes, calcium waves can travel across long dendritic distances, similar to electrical action potentials. We further observe that abortive regimes exist, which could be relevant for spike-timing dependent plasticity, as travel distances and wave velocities vary with changing intracellular architecture. For some of these regimes, analytic functions could be derived that fit the simulation data. In parameter spaces, that are non-trivially influenced by the three-dimensional calcium concentration profile, we were not able to derive such a functional description, demonstrating the mathematical requirement to model and simulate biochemical signaling in three-dimensional space.

摘要

通过简单扩散以及与移动和固定缓冲剂反应而传播的神经元钙信号仅限于细胞微区。借助从内部钙库(尤其是内质网)进行钙诱导的钙释放,细胞内钙信号能够传播的距离可能会显著增加。内质网这个细胞器可以被看作是细胞中的细胞,它能够通过肌浆网钙ATP酶泵隔离大量的胞质钙离子,并通过兰尼碱受体通道将它们选择性地释放到胞质溶胶中,从而导致钙波的形成。在本研究中,我们着手探究此类树突状钙波的基本特性,以及它们如何依赖于树突半径、内质网半径和内质网膜中兰尼碱受体密度这三个参数。我们证明,根据上述形态学和生理学参数,钙波存在稳定和夭折两种状态。在稳定状态下,钙波能够跨越较长的树突距离传播,类似于电动作电位。我们进一步观察到存在夭折状态,这可能与尖峰时间依赖性可塑性相关,因为传播距离和波速会随着细胞内结构的变化而改变。对于其中一些状态,可以推导出拟合模拟数据的解析函数。在受三维钙浓度分布非平凡影响的参数空间中,我们无法得出这样的函数描述,这表明在三维空间中对生化信号进行建模和模拟存在数学上的要求。

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