Mechanisms of valence selectivity in biological ion channels

Transmembrane ion channels play a crucial role in the existence of all living organisms. They partition the exterior from the interior of the cell, maintain the proper ionic gradient across the cell membrane and facilitate signaling between cells. To perform these functions, ion channels must be highly selective, allowing some types of ions to pass while blocking the passage of others. Here we review a number of studies that have helped to elucidate the mechanisms by which ion channels discriminate between ions of differing charge, focusing on four channel families as examples: gramicidin, ClC chloride, voltage-gated calcium and potassium channels. The recent availability of high-resolution structural data has meant that the specific inter-atomic interactions responsible for valence selectivity can be pinpointed. Not surprisingly, electrostatic considerations have been shown to play an important role in ion specificity, although many details of the origins of this discrimination remain to be determined. Received 4 September 2005; received after revision 17 October 2005; accepted 2 November 2005     

有无植物条件下明渠水流紊动特性对比

在可变坡水槽中，模拟了带枝杈植物对明渠水流的干扰作用，借助超声多普勒流速仪（ADV）测量了不同水深下垂线不同测点的瞬时流速，计算了各测点的三维时均流速、脉动强度及雷诺应力等紊动参数，通过与无植物干扰的明渠均匀流紊动特性进行对比，分析植物对水流紊动参数的影响规律。试验结果表明：在有植物明渠水流中，时均流速呈三区分布特征；脉动强度及雷诺应力均在植物顶部附近出现最大值；脉动强度明显增大，在3个方向上趋于接近；可以用植物顶部以上的雷诺应力分布推求摩阻流速。     

Interaction between bradykinin and voltage-sensitive sodium channels in myelinated nerve fibers

Summary The effects of externally and internally applied bradykinin on the excitability of single myelinated nerve fibers were studied. External bradykinin (10 M) slightly prolongs the action potential of a single myelinated nerve fiber; hence, when the fibers are stimulated by long-lasting pulses, this raises the frequency of repetitive firing in sensory fibers and evokes repetitive activity in motor fibers. Under voltage-clamp conditions, sodium channel inactivation is slowed, while sodium channel activation remains unaffected. Prolonged depolarization of th membrane leads to a maintained sodium current. The voltage dependence of the steady-state sodium current inactivation (h ) is shifted in the depolarized direction by 10 mV. Internally applied bradykinin produces a frequency-dependent block of the sodium current. The phenomena described here imply that more than one site on the sodium channel is modified by bradykinin.     

Characterization and relative abundance of maxi-chloride channels in Epstein-Barr virus (EBV) producer: B95-8 cells

Several Epstein-Barr virus (EBV)-transformed cell lines were used to investigate the pathogenesis of lymphoproliferative diseases and nasopharyngeal carcinoma. The studies focus on the events occurring inside the membrane. On only one occasion, the cell membrane of EBV-transformed B lymphocytes from a cystic fibrosis patient was found to express defective Cl channels (CFTR; Cystic Fibrosis Transmembrane conductance Regulator), as in the airway epithelial cell. No other type of channel in EBV-transformed cells has so far been investigated. In this study, the cell membrane of the B95-8 cell was examined by the patch-clamp technique and compared to the non-EBV-infected BJAB cell. The high conductance (300 pS) maxi-chloride (Cl) channel activity was the most frequently observed event in inside-out configurations. Under similar experimental conditions, we have found a significantly higher probability of detecting maxi-Cl channel activity on the cell membrane of B95-8 cells (69%) than on BJAB cells (27%), or as previously reported on resting murine B lymphocytes (38%) or intact human T lymphocytes (37%). The relative abundance of the maxi-Cl channel on B95-8 cells may be linked to EBV infection and/or secretory ability.     

The regulation of ion channels and transporters by glycolytically derived ATP

Glycolysis is an evolutionary conserved metabolic pathway that provides small amounts of energy in the form of ATP when compared to other pathways such as oxidative phosphorylation or fatty acid oxidation. The ATP levels inside metabolically active cells are not constant and the local ATP level will depend on the site of production as well as the respective rates of ATP production, diffusion and consumption. Membrane ion transporters (pumps, exchangers and channels) are located at sites distal to the major sources of ATP formation (the mitochondria). We review evidence that the glycolytic complex is associated with membranes; both at the plasmalemma and with membranes of the endo/sarcoplasmic reticular network. We examine the evidence for the concept that many of the ion transporters are regulated preferentially by the glycolytic process. These include the Na⁺/K⁺-ATPase, the H⁺-ATPase, various types of Ca²⁺-ATPases, the Na⁺/H⁺ exchanger, the ATP-sensitive K⁺ channel, cation channels, Na⁺ channels, Ca²⁺ channels and other channels involved in intracellular Ca²⁺ homeostasis. Regulation of these pumps, exchangers and ion channels by the glycolytic process has important consequences in a variety of physiological and pathophysiological processes, and a better understanding of this mode of regulation may have important consequences for developing future strategies in combating disease and developing novel therapeutic approaches. Received 20 July 2007; received after revision 30 July 2007; accepted 17 August 2007     

The effects of manganese and barium on the cardiac pacemaker current,i f,in rabbit sino-atrial node myocytes

Summary The isolation of ionic fluxes contributing to electric currents through cell membranes often requires block of other undesired components which can be achieved, among others, by divalent cations. Mn²⁺ and Ba²⁺ are often used, for example, to block Ca and K currents. Here we have investigated the effects of these two cations on the properties of the hyperpolarization-activated pacemaker current i_f, in rabbit sino-atrial node myocytes, as obtained by voltage clamp analysis. We find that 2 mM Mn²⁺ shifts the i_f activation curve by 3.2±0.3 mV towards more positive values. However, when 1 mM Ba²⁺ is also added, the positive shift is more than halved (1.3±0.2 mV). We find, too, that in the absence of blocking cations the ACh-induced i_f inhibition is slightly higher than in their presence. These results indicate that the alteration of i_f kinetic properties by Ba²⁺ plus Mn²⁺-containing solutions is minimal.     

Chemoelectrical signal transduction in olfactory sensory neurons of air-breathing vertebrates

When odorants bind to the sensory cilia of olfactory sensory neurons, the cells respond with an electrical output signal, typically a short train of action potentials. This review describes the present state of knowledge about the olfactory signal transduction process. In the last decade, a set of transduction molecules has been identified which help to explain many aspects of the sensory response. Odor-induced second-messenger production, activation of transduction channels, the central role of the ciliary Ca²⁺ concentration, as well as mechanisms that mediate adaptation, are all qualitatively understood on the basis of a consistent scheme for chemoelectrical transduction. This scheme, although necessarily incomplete, can serve as a working model for further experimentation which may reveal kinetical aspects of signal transduction processes in olfactory sensory neurons.     

基于二维导频的OFDM系统信道估计算法研究

提出了基于一种离散傅立叶变换与一维维纳滤波联合的信道估计算法,相比线性内插与一维维纳滤波联合的估计算法仅利用相邻导频获得导频间信道估计,该算法通过插入二维导频对数据分块,利用每个分块的接收数据进行信道估计,从而提高了信道估计的性能.与二维维纳滤波算法相比,该算法在估计性能接近的情况下,计算复杂度大大降低.     

Patch clamp technique and biophysical study of membrane channels

Summary The present work describes the patch clamp technique, which first allowed the recording of single channel currents in biological membranes. In particular, it describes procedures for preparation and applications of the four different patch clamp configurations. Briefly, the cell-attached configuration is widely used for investigating channel modulation by transmitters acting via second messengers. The cell-free configurations (inside-out and outside-out), complementary to one another with respect to the orientation of the membrane surface, are particularly indicated for the study of the biophysics (kinetics, conductivity, selectivity, mechanism of permeation and block) of ionic channels. Finally, the whole-cell configuration which, because of the remarkable feature that it allows voltage clamp of very small cells, has given access to a number of physiologically important preparations never studied before.     

Are stretch-sensitive channels in molluscan cells and elsewhere physiological mechanotransducers?

Single-channel recordings of dozens of cell types, including invertebrate (molluscan) and vertebrate heart cells, reveal stretch-sensitive ion channels. The physiological roles of these channels are undoubtedly diverse but it is usually assumed that the roles they play are related to the channels' mechanosensitive gating. Whether this assumption is valid remains to be seen. Attempts to connect the single-channel observations with the mechanical aspects of physiological or developmental processes are discussed. In the case of molluscan cells, recent work suggests that their stretch channels have physiological functions unrelated to mechanosensitive gating.     

AM信号确认算法研究与仿真

通过分析短波段AM广播信号调制特性，定义了调制信号上下边带频谱相关系数和调制信号与包络检波信号频谱相关系数，并以语音检测相关参数作为辅助。由此提出一种对AM广播信号进行“身份验证”的信号确认算法。基于短波标准信道的仿真实验表明，所定义的两个参数对噪声和信道滤波鲁棒，该算法可直接应用于实际工程环境，具有重要应用价值。     

淹没状态下河道植物偏斜高度与糙率的关系

利用室内变坡水槽,模拟了复式河道滩地3种植物对漫滩水流的干扰作用,并借助声学多普勒测速仪（ADV）施测了不同垂线、不同测点的瞬时流速,计算了不同条件下的河道糙率。基于水动力及植物柔性变形分析,建立了淹没状态下的植物河道糙率计算的基本关系,反映出糙率值不仅与水流动力条件有关,还与植物类型、淹没高度、布置及其自身力学性能有关,同时,利用试验资料及理论分析成果,进一步获取了植物河道的附加糙率值,借此分析与评价河道植物对水流阻力的影响程度。     

Solute traffic across mammalian peroxisomal membrane – single channel conductance monitoring reveals pore-forming activities in peroxisomes

Mouse liver peroxisomes were isolated by centrifugation in a self-generated Percoll gradient followed by an Optiprep density gradient centrifugation. Peroxisomes contributed 90–96% of the total protein content in the fraction, as confirmed by marker enzyme assays, protein pattern in SDS-PAGE, immunoblotting, and electron microscopy. Solubilized peroxisomal membrane proteins were reconstituted into a planar lipid bilayer. A single-channel conductance monitoring of the reconstituted lipid bilayer revealed the presence of two pore-forming components with a conductance in 1 M KCl of 1.3 nS and 2.5 nS. Control experiments with fractions enriched in mitochondria, lysosomes, and fragments of endoplasmic reticulum showed that the peroxisomal channel-forming activities were not due to admixture of isolated peroxisomes with other cellular organelles. The peroxisomal channels were well preserved in membrane preparations but became unstable after solubilization from the membranes by detergent. Received 27 May 2005; received after revision 23 September 2005; accepted 11 October 2005     

TD-SCDMA系统中引入阈值信噪比的信道估计

采用联合检测和智能天线等技术是TD-SCDMA移动通信系统的优势之一,但这些技术的实现必须以准确的信道估计为前提.本文探讨了适合于TD-SCDMA系统的信道估计算法,分析了一种加入阈值信噪比的信道估计算法原理.通过上行链路的模拟仿真表明,该信道估计算法的信道响应更接近理想值,有利于提高系统性能.     

压缩感知非凸优化超宽带信道估计方法研究

超宽带信号由于传输路径较复杂且功率谱密度较低,准确的信道估计十分重要．但是由于其带宽较宽,难以直接采样．压缩感知理论提供了一种可行的低速采样方法．目前的压缩感知超宽带信道估计方法一般采用l1范数约束的凸优化形式或无稀疏性的l2范数约束形式,对目标向量的稀疏性约束不强,而拥有最强稀疏性的l0范数又缺少有效的重构算法．针对上述问题,本文设计一种基于非凸优化算法的压缩感知超宽带信道估计方法．首先将目标函数设置成l,范数约束的非凸优化形式,然后利用凸函数较易求得极值的性质,将原非凸函数组合成为凸函数形式的目标函数,并通过每步迭代凸函数对非凸函数的逼近来求解目标函数,进而估计出原信道．由于lp范数更接近于l0范数,所以对目标向量稀疏性的约束更强．实验结果表明,所提方法相对于现有的压缩感知超宽带信道估计方法能够有效降低重构误差．     

Voltage-gated proton channels

The history of research on voltage-gated proton channels is recounted, from their proposed existence in dinoflagellates by Hastings in 1972 and their demonstration in snail neurons by Thomas and Meech in 1982 to the discovery in 2006 (after a decade of controversy) of genes that unequivocally code for proton channels. Voltage-gated proton channels are perfectly selective for protons, conduct deuterons half as well, and the conductance is strongly temperature dependent. These properties are consistent with a conduction mechanism involving hydrogen-bonded-chain transfer, in which the selectivity filter is a titratable amino acid residue. Channel opening is regulated stringently by pH such that only outward current is normally activated. Main functions of proton channels include acid extrusion from cells and charge compensation for the electrogenic activity of the phagocyte NADPH oxidase. Genetic approaches hold the promise of rapid progress in the near future.     

Conotoxins of the O-superfamily affecting voltage-gated sodium channels

The venoms of predatory cone snails harbor a rich repertoire of peptide toxins that are valuable research tools, but recently have also proven to be useful drugs. Among the conotoxins with several disulfide bridges, the O-superfamily toxins are characterized by a conserved cysteine knot pattern: C-C-CC-C-C. While ω-conotoxins and κ-conotoxins block Ca²⁺ and K⁺ channels, respectively, the closely related δ- and μO-conotoxins affect voltage-gated Na⁺ channels (Na_v channels). δ-conotoxins mainly remove the fast inactivation of Na_v channels and, thus, functionally resemble long-chain scorpion α-toxins. μO-conotoxins are functionally similar to μ-conotoxins, since they inhibit the ion flow through Na_v channels. Recent results from functional and structural assays have gained insight into the underlying molecular mechanisms. Both types of toxins are voltage-sensor toxins interfering with the voltage-sensor elements of Na_v channels. Received 27 December 2006; received after revision 30 January 2007; accepted 19 February 2007     

Two serotonin-sensitive potassium channels in the identified heart excitatory neurone of the African giant snail,Achatina fulica Fèrussac

Summary By the patch clamp experiments, two serotonin-sensitive K⁺ channels (SL-channel and SS-channel) were demonstrated in the identified heart excitatory neurone (PON) of the African giant snail,Achatina fulica Fèrussac. The activities of both channels could be recorded in the steady state and those activities disappeared on application of 5-HT.     

基于节点状态的多接口多信道WMN信道分配算法

多接口多信道无线Mesh两络信道分配的目的在于提升网络容量以及保持网络连通的同时,降低干扰,增强信道负载平衡.由此,提出一种基于节点状态的信道分配方案.该方案是一种基于优先级的多项式时间贪婪混合式算法.NS2仿真结果表明,该算法不仅可以较好地解决信道负载平衡,提升网络容量,而且即使在节点接口的数量少于有效信道数量时,也能使信道得到有效的分配,保证网络的连接通畅.     

Down-regulation of sodium current in chronic heart failure: effect of long-term therapy with carvedilol

Evidence has accumulated recently about the importance of alterations in Na⁺ channel function and slow myocardial conduction for arrhythmias in the infarcted and failing heart. The present study tested a hypothesis that Na⁺ current (I_Na/C) density decreases in chronic heart failure (HF) and that Na⁺ channel (NaCh) functional density can be restored by long-term therapy with carvedilol, a mixed α- and β-adrenergic blocker. Studies were performed using a canine model of chronic HF produced in dogs by sequential intracoronary embolizations with microspheres. HF developed approximately 3 months after the last embolization (left ventricle, LV, ejection fraction = 28 ± 1 %). Ventricular cardiomyocytes (VCs) were isolated enzymatically from LV mid-myocardium, and I_Na was measured by whole-cell patch-clamp. The maximum I_NA/C was decreased in failing (n = 19) compared to normal (n = 12) hearts (33.1 ± 1.6 vs 48.5 ± 5.1 pA/pF, mean ± SE, p < 0.001). The steady-state inactivation and activation of I_Na remained unchanged in failing compared to normal hearts. Long-term treatment with carvedilol (1 mg/kg, twice daily for 3 months) normalized I_Na/C in dogs with HF. I_Na/C in HF dogs (n = 6) treated with carvedilol was higher compared to that of non-treated HF dogs (n = 6) (49.4 ± 0.9 vs 29 ± 4.8 pA/pF, p < 0.007). In vitro culture of VCs of failing hearts for 24 h did not restore I_Na/C. However, I_Na/C was partially restored when VCs were incubated for 24 h with BAPTA-AM, an intracellular Ca²⁺ buffer. Thus, we conclude that experimental chronic HF in dogs results in down-regulation of the functional density of NaCh that can be restored by long-term therapy with carvedilol. The mechanism of NaCh down-regulation in HF may be linked to poor Ca²⁺ handling in this stage of disease. Received 4 June 2002; received after revision 1 July 2002; accepted 17 July 2002 RID="*" ID="*"Corresponding author.