基于小波变换的离子单通道信号的分析方法

在单通道信号处理中引入尺度能量分布的概念 ,利用小波变换 ,通过提取具有特征频率的高频信号 ,可以在不失真的条件下将单通道信号清晰地检测出来 ,消除噪声干扰。本文提供的方法在离子通道信号处理中具有较普遍的意义     

剪切应力诱导成骨细胞钾离子通道开放的研究

目的探索成骨细胞如何应答机械应力刺激,并将刺激信号转导进入细胞内,从而调节骨改建的分子机制。方法利用膜片钳及自行设计的流动小室系统对体外培养的单层Wister大鼠乳鼠成骨细胞在可控流体剪切应力作用下诱导细胞膜K 通道的开放进行了初步研究。结果剪切应力作用后,成骨细胞膜上K 电流明显增大。结论成骨细胞细胞膜上存在剪切应力敏感的K 通道,流动剪切应力可以通过影响成骨细胞膜上的K 通道的开放引起穿细胞的离子通透性的增加,进而引起细胞内Ca2 浓度变化,同时诱导细胞内钙调节机制的激活,这些变化都可以进一步引起细胞信号转导机制的激活。     

Ion channels and lymphocyte activation

The ion channels expressed by T lymphocytes play key roles in the control of the membrane potential and calcium signaling, thereby affecting signal transduction pathways that lead to the activation of these cells following antigenic stimulation. Disruption of these pathways can attenuate or prevent the response of T-cells to antigenic challenge resulting in immune suppression. Studies using ion channel blockers of high affinity and specificity have shown that this interference can be achieved at the level of ion channels. Suppression of immune functions by channel blockers has been demonstrated in vitro and in vivo. New information about the molecular structure of ion channels facilitates the design of more potent and more specific inhibitors. Thus, T-cell ion channels are likely to serve as targets for immunomodulatory drugs in the near future. Here, the biophysical properties, tissue distribution, regulation of expression, molecular pharmacology and role in T-cell activation of the voltage-gated Kv1.3 and the Ca(2+)-activated IKCa1 potassium channels and those of the Ca(+) release-activated Ca(2+) (CRAC) channel are reviewed.     

细胞膜离子单通道信号的频域分析方法

利用离散小波变换构造尺度能量分布函数 (Power distribution function,PDF) ,分析单通道信号的频域特征 ;同时采用功率密度谱 (Power spectral density,PSD)方法进行分析。结果表明 ,基于离散小波变换 (Discretewavelet transform,DWT)的尺度能量分布是一种非常有效的单通道信号的频域分析方法。     

Stochastic behaviour of ion channels in varying conditions

The opening and closing of a single ion channel can be describedas the aggregation into two sets of states, open and shut, ofan underlying Markov process with a finite number of states.In this paper we consider an inhomogeneous process due to changingphysical conditions, in particular a pulse of activity in whichthe transition rates during the pulse differ from those obtainingboth before and after the pulse. Outside the pulse the chaincontains an absorbing shut subset, so that no activity is observedbefore the pulse and, almost surely, at most a finite numberof openings are generated by the pulse. We consider, in particular,the probability distribution of first latency (the time to firstopening) and the distribution of the total activation time.We take into account the phenomenon of time-interval omission,when short open or shut times fail to be observed.     

基于HMM的低信噪比离子通道信号的恢复及参数估计

细胞膜离子单通道信号是皮安级的随机电流 ,膜片钳技术可以记录这些信号。一般认为它是一阶的、状态有限的 Markov过程。某些种类的离子通道 ,电流信号特别微弱 ,完全淹没在背景噪声中 ,传统的膜片钳技术很难检测到 ,只能运用数学方法恢复和估计。在低采样频率情况下 ,由于混叠效应 ,可认为背景噪声是白色的 ;在高采样频率条件下 (高于奈奎斯特频率 ) ,背景噪声是有色的。本文分别综述了白色背景噪声条件下基于隐式 Markov模型和有色背景噪声条件下基于隐式矢量 Markov模型的低信噪比离子单通道信号的恢复和参数估计 ,主要包括前后向算法、EM算法等     

人脐静脉内皮细胞膜上钙和钾离子通道

目的：观察体外培养人脐静脉内皮细胞膜上钙离子（Ｃａ＾２＋）通道和Ｃａ＾２＋激活的钾离子（ｋｃａ）通道。方法：膜片钳单通道记录技术。结果：体外培养人脐静脉内皮细胞上含有Ｃａ＾２＋通道和Ｋｃａ通道,但其通道分布概率和开放概率均不高．结论：人脐静脉内皮细胞作为一种非兴奋性细胞。其细胞膜上含有的Ｃａ＾２＋通道和Ｌｃａ通道,对细胞浆内Ｃａ＾２＋浓度的维持、Ｃａ＾２＋补充来源和细胞电位的维持等均具有重要意义,     

NMDA receptor kinetics and synaptic function

Presynaptic release of L-glutamate mediates neurotransmission at most excitatory synapses in the vertebrate central nervous system. At the postsynaptic membrane, glutamate binds to two classes of ligand-gated ion channels, AMPA receptors and NMDA receptors. These channels are the basis of the two kinetically distinct components of the excitatory postsynaptic current (epsc). The slower synaptic conductance is mediated by NMDA receptor channels which, after binding glutamate, activate slowly and can remain activated for several hundred milliseconds. The average latency between glutamate binding and channel opening is at least several milliseconds and may be much longer. If the time to first opening is short many fewer channels would be required at each synaptic site to account for the amplitude of the NMDA receptor component of spontaneous miniature epscs, than if the time to first opening is very long.     

独立分量分析技术在EEG工频干扰分离中的应用

工频干扰是脑电图(EEG)中常见噪声，严重影响EEG-信号的提取和分析。通过比较Fastica、Extended Infomax、EGLD、Pearson—ICA等四种独立分量分析(ICA)算法和奇异值分解(SVD)技术用于分离EEG中工频干扰的效果，确证ICA方法有很好的抗干扰性，而常用的SVD技术则难以奏效；其中推广的最大熵(Extended Info—max)ICA算法有较好的收敛性，文中使用该算法成功地从16导联早老性痴呆症患者EEG信号中(含混入的工频干扰，最低信噪比约为0dB)分离出工频干扰。ICA在生物医学信号处理特别是临床医学工程中潜在着重要应用前景和研究价值。     

Hydrogen ions control synaptic vesicle ion channel activity in Torpedo electromotor neurones

During exocytosis the synaptic vesicle fuses with the surface membrane and undergoes a pH jump. When the synaptic vesicle is inside the presynaptic nerve terminal its internal pH is about 5.5 and after fusion, the inside of the vesicle comes in contact with the extracellular medium with a pH of about 7.25. We examined the effect of such pH jump on the opening of the non-specific ion channel in the synaptic vesicle membrane, in the context of the post-fusion hypothesis of transmitter release control. The vesicles were isolated from Torpedo ocellata electromotor neurones. The pH dependence of the opening of the non-specific ion channel was examined using the fused vesicle-attached configuration of the patch clamp technique. The rate of opening depends on both pH and voltage. Increasing the pH from 5.5 to 7.25 activated dramatically the non-specific ion channel of the vesicle membrane. The single channel conductance did not change significantly with the alteration in the pH, and neither did the mean channel open time. These results support the hypothesis that during partial fusion of the vesicle with the surface membrane, ion channels in the vesicle membrane open, admit ions and thus help in the ion exchange process mechanism, leading to the release of the transmitter from the intravesicular ion exchange matrix. This process may have also a pathophysiological significance in conditions of altered pH.     

超声多普勒信号准平稳分段的研究

超声多普勒音频信号是一种非平稳时间序列 ,其功率谱是时变谱。为了能够准确有效地计算它的功率谱 ,要兼顾时间分辨力和时间窗截断效应。以前采用 10ms固定长度时间窗进行功率谱估计虽有其合理性但并不完善。本文利用线性调频信号研究超声多普勒信号的非平稳特性 ,并在此基础上得出了超声多普勒信号准平稳时间段随心动时相不同而不同的结论 ,为超声多普勒信号谱分析的时间窗选取提供依据。     

Benzodiazepine interactions with GABA receptors

Benzodiazepines (BZs) produce most, if not all, of their pharmacological actions by specifically enhancing the effects of endogenous and exogenous GABA that are mediated by GABAA receptors. This potentiation consists in an increase of the apparent affinity of GABA for increasing chloride conductance without increase in its efficacy and, on the single chloride channel level, seems to be the result of an increased probability of channel opening events. Recent studies indicate that the BZR is a site on the GABA receptor (GABA-R)-chloride channel complex, through which the gain of the signal transducer function of the latter is allosterically modulated. The unique feature of this drug receptor, which is located on a neurotransmitter receptor-gated ion channel, is its specific interaction with three classes of ligands. Agonists, competitive antagonists and inverse agonists at BZR, respectively increase, do not alter and reduce the gain of the GABA-R function. Compounds have been found that cover a whole spectrum of transition between the two extremes (partial agonists, partial inverse agonists) and for which interesting therapeutic applications can be foreseen.     

ClC-3氯通道蛋白磷酸化及其功能的研究进展

细胞容积调节广泛参与细胞的各种生理病理过程,如上皮细胞物质转运、物质代谢、细胞兴奋性、激素释放、细胞迁移、细胞增殖及细胞坏死凋亡等[1, 2].在低渗环境刺激下,容积激活性氯通道参与细胞容积调节,对维持细胞容积起着重要调节作用.     

Biophysical properties and regulation of GABAA receptor channels

When GABA binds to the GABA_A receptor, bursts of chloride ion channel openings occur, resulting in membrane hyperpolarization. Barbiturates increase current by increasing mean channel open time, and the convulsant drug picrotoxin decreases current by decreasing mean channel open time. The two drugs bind to allosterically coupled sites on the receptor to regulate channel gating. Benzodiazepines increase and β-carbolines decrease channel opening frequency by binding to the benzodiazepine receptor on GABA_A receptor channels. Neurosteroids increase current by increasing mean channel open time and opening frequency, possibly by interacting with a specific site on the GABA_A receptor. The convulsant drug penicillin reduces current by producing open channel block. The GABA_A receptor subunits contain consensus sequences for phosphorylation by cAMP-dependent kinase, C kinase and tyrosine kinase. The functional consequences of receptor phosphorylation remain unclear. In future studies the use of molecular biological and single channel recording techniques should allow characterization of the properties of GABA_A receptor channels, the role of receptor phosphorylation and the specific mechanisms of actions of regulatory drugs.     

心电信号零相位数字滤波

分析了零相位数字滤波的原理 ,通过对实测心电信号中 5 0Hz工频干扰的抑制结果表明 ,该方法对心电信号的滤波性能优于普通数字滤波方法 ,特别是对心电信号中QRS波群具有更好的滤波效果 ,在心电信号的处理、分析和自动识别中具有很高的应用价值     

血管活性肠肽对人脐静脉内皮细胞Ca~(2+)及其膜通道的调控

目的　观察血管活性肽 (VIP)对人脐静脉内皮细胞 (HUVEC)膜上Ca2 + 通道及胞浆内游离Ca2 +([Ca2 + ]i)的调控作用。方法　应用共聚焦激光扫描显微术 (CLSM)和膜片钳单通道记录技术对体外培养HU VEC胞浆内 [Ca2 + ]i、膜上Ca2 + 通道开放情况进行观察。结果　VIP促使HUVEC胞膜上Ca2 + 通过道的开放概率和胞浆内 [Ca2 + ]i 均明显升高。结论　IVP对HUVEC胞浆内 [Ca2 + ]i的调节可能除通过细胞内储存的Ca2 +释放外还依赖细胞膜上Ca2 + 通道开放 ,从而达到其调节效应     

P物质对人脐静脉张力及内皮细胞Ca2+的调控及其机制

目的：观察P物质（SP）对人脐静脉张力的调节及其对体外培养人脐静脉内皮细胞（HUVEC）膜上Ca^2 通道及胞浆内游离Ca^2 浓度[(Ca^2 )i]的调控作用。方法：应用常规生理记录仪，记录SP对人脐静脉张力的影响，用共聚焦激光扫描显微术和膜片钳单通道记录技术对体外培养HUVEC胞浆内（Ca^2 )i、膜上Ca^2 通道开放情况进行观察。结果：SP具有内皮依赖性舒张人脐静脉的作用，促使体外培养HUVEC胞膜上Ca^2 通道开放和胞浆内（Ca^2 ）i明显升高。结论：SP对人脐静脉张力的舒张作用可能通过HUVEC胞浆内储存的（Ca^2 ）i释放和膜上Ca^2 通道开放，达到其调节效应。     

What single-channel analysis tells us of the activation mechanism of ligand-gated channels: the case of the glycine receptor

Glycine receptors are, in several ways, the member of the nicotinic superfamily that is best-suited for single-channel recording. That means that they are ideal for testing ideas about how activation proceeds in a ligand-gated ion channel from the binding of the agonist to the opening of the channel. This review describes the quantitative characterization by single-channel analysis of a novel activation mechanism for the glycine receptor. The favourable properties of the glycine receptor allowed the first detection of a conformation change that follows the binding of the agonist but precedes the opening of the channel. We used the term 'flipping' to describe this pre-opening conformational change. The 'flipped' state has a binding affinity higher than the resting state, but lower than the open state. This increased affinity presumably reflects a structural change near the agonist binding site, possibly the 'capping' of the C-loop. The significance of the 'flip' activation mechanism goes beyond understanding the behaviour and the structure–function relation of glycine channels, as this mechanism can be applied also to other members of the superfamily, such as the muscle nicotinic receptor. The 'flip' mechanism has thrown light on the question of why partial agonists are not efficacious at keeping the channel open, a question that is fundamental to rational drug design. In both muscle nicotinic and glycine receptors, partial agonists are as good as full agonists at opening the channel once flipping has occurred, but are not as effective as full agonists in eliciting this early conformational change.