前包钦格复合体中钙动力学对放电模式的影响

本文以前包钦格复合体中两个耦合神经元为研究对象,并考虑钙离子动力学的神经元动力学模型。利用相平面分析、分岔分析和快慢动力学分析等方法,研究钙离子动力学和控制钙激活的非特异性阳离子电流的电导对前包钦格复合体的放电模式的影响,并从动力学的角度解释了其放电活动产生及其转迁的机制。结果表明钙离子的周期性波动和非特异性阳离子电流都会影响簇放电的类型,钙离子的周期性波动是产生复杂簇放电的关键因素。     

低温等离子体对 MCF-7 乳腺癌细胞的 化疗增敏作用

为了改善肿瘤细胞对化疗药物的耐药性,该文提供了一种通过促进细胞对药物的摄取来增敏 化疗的方法。低温等离子体作用肿瘤细胞后,培养基内的活性氧显著升高,进一步改变了细胞膜通透 性,使得外源活性氧及钙离子进入细胞内而诱发细胞凋亡。与此同时,细胞膜通透性的改变还可以增 加细胞对化疗药物的摄取,进一步提高了肿瘤细胞杀伤效率。结果显示,细胞经过等离子体处理以 后,显示出 20% 的细胞杀伤效率。阿霉素作为常见的抗肿瘤药物,在 4 μg/mL 的浓度下可以杀伤 46% 的细胞;而联合等离子体治疗后,细胞杀伤效率增加至 88%,显著增敏了阿霉素的化疗效果。另外, 等离子体联合金纳米棒治疗后,显示出 90% 的细胞杀伤效率,相对于单独使用金纳米棒(64%)的效果 更为显著。因此,等离子体在引发细胞凋亡的同时,可以通过细胞膜通透性的改变,增加细胞对化疗 药物的摄取,进而增敏化疗效果。     

基于微流控芯片的钙离子浓度检测系统的实现

在细胞内物质定量分析中引入微流控芯片.利用微流控芯片完成细胞的培养、染色、试剂的进给等生物实验功能.设计了用于细胞内钙离子浓度检测的微流控荧光检测系统.通过双波长激发,利用荧光检测系统完成荧光强度和图像的采集.同时研究比值荧光法,计算出定量检测的钙离子浓度.实验结果表明,此检测装置可靠性高,检测结果准确.这一研究,提供了一种细胞检测新手段.为细胞研究提供更加便捷的细胞培养、检测、试剂进给一体化检测装置.     

聚乳酸三维微结构条件下人神经母细胞瘤细胞电压依从式钙通道的功能响应性

以紫外光光刻、硅蚀刻及软光刻技术制备了聚乳酸(poly-L-lactide,PLLA)三维微小凹图式,考察人神经母细胞瘤细胞(SH-SY5Y)在微小凹结构上的生长与分布行为。以共聚焦显微技术结合钙离子荧光染料Calcium Green-1,AM评价SH-SY5Y细胞在PLLA三维微小凹图式和平面基底上电压依从式钙离子通道(VGCCs)的功能响应性。实验发现,分布在微小凹顶部的细胞为二维生长方式,凹内侧壁的为三维生长方式,凹内底部的为边界二维生长方式;以50 mmol/L高钾溶液去极化刺激发现,三维及边界二维细胞VGCCs阳性响应比率为75%和81%,较平面培养的91.2%明显降低。上述结果表明,PLLA三维微结构及细胞生长行为是影响SH-SY5Y细胞VGCCs功能响应性的重要因素,微小凹图式是模拟神经细胞三维生长环境进而构建三维细胞生物传感器的有效途径。     

脑皮层神经网络的线性时滞反馈控制

神经元的病态同步放电会破坏大脑的正常功能, 导致癫痫和帕金森等生理疾病. 本文采用神经元二维映射模型构建一个脑皮层神经网络, 当神经元之间的耦合强度超过某一阈值时, 网络中所有神经元同步放电. 通过施加线性时滞反馈控制, 可以有效的消除这种同步状态, 且不改变神经元本身的放电特性. 仿真结果表明线性时滞反馈 可以实现对脑皮层神经网络的去同步化控制, 且对刺激参数的变化具有鲁棒性.     

基于多变量符号转移熵的癫痫脑电分析

大脑神经元细胞群的异常同步放电是癫痫的病因,这种异常放电是目前诊断癫痫的重要依据。利用复杂度理 论来分析癫痫信号已经成为研究热点,而符号转移熵是反应系统混乱程度的一种非线性指标,在研究癫痫脑电信号特征的提取中有重要的作用。符号转移熵一般都是用来衡量两 个变量之间的动力学特征及方向性信息,忽略了多个变量之间相互作用。本文基于多变量符号转移熵研究分析了癫痫脑电信号,实验中将原始信号符号化后通过数值分析,对导联信号及信号长度的选取以及稳健性分析,表明该方法能够对正常人与癫痫病人的脑电信号进行显著区分,且该算法稳健可靠,该研究结果对临床辅助诊断有帮助。     

耦合pre-B tzinger复合体神经元中混合簇放电的多时间尺度动力学分析

Pre-B tzinger复合体是新生哺乳动物呼吸节律起源的关键部位,是呼吸节律产生的中枢.本文以pre-B tzinger复合体中两个耦合的神经元为研究对象,并考虑钙离子动力学的耦合神经元模型.利用多时间尺度动力学、快慢尺度分解和分岔分析,研究混合簇同步放电模式及其产生机制,并研究了耦合神经元同相和反相簇放电类型及其同步转迁.结果表明钙离子的周期性波动对混合簇放电模式的产生有极大的影响,钙离子波动导致的时间尺度变化及分岔曲线相对位置的改变是混合簇放电产生的主要原因.本文的研究对认识pre-B tzinger中大规模网络的动力学有着重要的意义,为进一步探索呼吸节律的产生机制提供了一些有益的思考和见解.     

应用Simulink模拟耦合神经元的同步活动

癫痫是一组由神经元异常放电所引起的短暂中枢神经系统功能异常为特征的慢性脑部疾病。其发病的原因正是由于神经元集体的异常同步放电行为所致。以FitzHugh-Nagumo神经元为例,使用simulink对耦合神经元的同步活动进行模拟,供相关研究人员进行研究。     

一种胶质细胞偶联人工神经网络模型

受到生物大脑神经胶质细胞和神经元互作用机制的启示,提出一种胶质细胞偶联人工神经网络(Glia-Coupled Artificial Neuron Networks, GCANNs)模型.对当前人工神经网络模型中的基本单元—神经元进行扩展,将每一个神经元连接一定数量的胶质细胞作为网络基本单元,通过神经元和胶质细胞的相互作用模型进行基本单元各元素的计算和更新,最后通过遗传算法对该模型的参数、拓扑结构进行优化.该网络模型能反应胶质细胞和神经元之间的双向通讯机制,更接近神经系统各元素之间的信息处理方式.实验表明,该模型能提升网络学习性能,在图像、文本等的分类任务上表现出比传统人工神经网络更高的准确率.此外,基于遗传算法的网络优化实验表明,为获得更高的适应度,大部分神经元都选择了与一定数量的胶质细胞“相连”,说明胶质细胞偶联的模型是经过了“自然进化、优胜劣汰”的更优模型.该模型能为构建更符合大脑工作机理的神经网络提供新的思路和方法,也能反向启发和推进神经科学研究.     

Pre-Botzinger复合体中耦合神经元簇同步模式及转迁的分岔分析

Pre-Botzinger复合体中兴奋性神经元节律性簇放电与呼吸节律的产生关系密切.泄漏电流对神经元簇放电具有重要的调节作用.本文利用双参数分岔分析和快慢变量分离等方法,研究了泄漏电流对耦合神经元簇同步模式及其转迁机制的影响.结果表明,在不同初始条件下,当泄漏电导改变时耦合神经元分别表现为同相“fold/homoclinic”型、“subHopf/homoclinic”型和反相“fold/fold cycle”型和“subHopf/fold cycle”型簇放电.本文的研究为进一步探索呼吸节律的产生机制提供了一些见解.     

Minimal model for intracellular calcium oscillations and electrical bursting in melanotrope cells of Xenopus laevis

A minimal model is presented to explain changes in frequency, shape, and amplitude of Ca2+ oscillations in the neuroendocrine melanotrope cell of Xenopus Laevis. It describes the cell as a plasma membrane oscillator with influx of extracellular Ca2+ via voltage-gated Ca2+ channels in the plasma membrane. The Ca2+ oscillations in the Xenopus melanotrope show specific features that cannot be explained by previous models for electrically bursting cells using one set of parameters. The model assumes a KCa-channel with slow Ca2+-dependent gating kinetics that initiates and terminates the bursts. The slow kinetics of this channel cause an activation of the Kca-channel with a phase shift relative to the intracellular Ca2+ concentration. The phase shift, together with the presence of a Na+ channel that has a lower threshold than the Ca2+ channel, generate the characteristic features of the Ca2+ oscillations in the Xenopus melanotrope cell.     

SU-8 microstructure for quasi-three-dimensional cell-based biosensing

A quasi-three-dimensional (quasi-3-D) cell-based biosensor platform microfabricated from SU-8 has been developed and characterized. In this work, SH-SY5Y human neuroblastoma cells were integrated with SU-8 microfabricated microwells with diameters of 100 μm. SH-SY5Y cells were differentiated with 1 mM dibutyryl cAMP and 2.5 μM 5-bromodeoxyuridine. Voltage-gated calcium channel (VGCC) function of SH-SY5Y cells cultured within the microwells (quasi-3-D) versus those cultured on the SU-8 planar substrates (2-D) was evaluated by confocal microscopy with a calcium fluorescent indicator, Calcium Green-1. In response to 50 mM high K⁺ depolarization, cells in microwells were less responsive in terms of increase in intracellular Ca²⁺ in comparison to cells on 2-D substrates. This study shows that VGCC function of cells within SU-8 microwells was indeed different from that of cells on planar SU-8 surfaces, suggesting that SU-8 microstructure did affect SH-SY5Y cell differentiation with respect to VGCC function and that high-aspect-ratio microstructures are not merely “folded” 2-D structures. Furthermore, these results are consistent with previous 2-D/3-D comparative studies carried out in polymer scaffolds and support the hypothesis that cell calcium dynamics on 2-D substrates may be exaggerated. Overall, this work is supportive of SU-8 micropattern as a viable platform for engineering a quasi-3-D cell culture system for cell-based biosensing against drugs for VGCCs.     

The astrocyte as a gatekeeper of synaptic information transfer

We present a simple biophysical model for the coupling between synaptic transmission and the local calcium concentration on an enveloping astrocytic domain. This interaction enables the astrocyte to modulate the information flow from presynaptic to postsynaptic cells in a manner dependent on previous activity at this and other nearby synapses. Our model suggests a novel, testable hypothesis for the spike timing statistics measured for rapidly firing cells in culture experiments.     

Calcium dynamics in cardiac myocytes: a model for drugs effect description

Ca²⁺ dynamics and handling in cardiomyocytes are critical for both metabolism and contraction of the heart. Action potentials involve membrane and subcellular components. In response to membrane depolarization during an action potential, L-type Ca²⁺ channels open, allowing the influx of Ca²⁺ into a restricted subspace where it triggers Ca²⁺ release from the sarcoplasmic reticulum (SR) via ryanodine-sensitive Ca²⁺ channels (RyRs). This results in a global increase in the cytosolic Ca²⁺ concentration which triggers contraction through the contractile proteins. Relaxation follows the reuptake of Ca²⁺ into the SR by the Ca²⁺ pump in the SR (SERCA) or its extrusion from the cell essentially ensured by the Na–Ca exchanger. A model of Ca²⁺ handling model developed in a precedent work give us quite good results but its not sufficient to explain the cell behaviour in presence of some specific substance like arachidonic acid. In order to explain this difference the authors have developed a new model taking into account a modification of some specific components of the SR.     

火焰原子吸收法测定钙时某些化学干扰的计算消除方法

本文研究了火焰原子吸收法测定钙时某些化学干扰的计算消除方法，提出了一个普遍性的数学模型，本文旨在研究包括待测元素和干扰元素的两元体系中干扰效应的一些规律，筛选出表达其相互关系的数学模型，经测定混合液中钙的含量，表明计算法能较好地消除磷酸根和铝对钙的化学干扰。     

Modeling the steady-state behavior of the Ca2+ -Mg2+ -ATPase pump of sarcoplasmic reticulum

A FORTRAN computer program capable of calculating the steady-state behavior of the Ca2+ -Mg2+-ATPase pump of skeletal sarcoplasmic reticulum under all conditions of reactant and product concentrations is described. The model describes the behavior of the enzyme in terms of occupation of three binding sites: (a) a translocator site which can bind Ca2+, K+, H+, or Mg2+, (b) an ATP/ADP binding site, and (c) a phosphorylation and phosphate binding site. The translocator site can move across the membrane in the Ca2+-laden and K+ + H+-laden form, thereby accomplishing Ca2+ for K+ + H+ countertransport. The rate constants for ion binding and the translocation reactions vary as a function of translocator orientation, ATP and ADP occupancy, phosphorylation, and phosphate binding. Rate constants for the binding and the reactant and product concentrations and association reactions and other transformations between states of the enzyme are entered and the computer program solves for the steady-state concentrations of all states of the enzyme and for the turnover number of the enzyme. The program contains a matrix of differential equations for creation and destruction of all states of the enzyme using the steady-state assumption together with the rule of conservation of the total enzyme. The matrix of equations and states is solved by Gaussian elimination. The program presents the distribution of enzyme states in histogram fashion and is capable of presenting the concentration of a particular state or the rate of turnover as a function of any of the reactant or product concentrations. Three demonstrations of the utility of the program and predictive power of the model are given.