Influence of non-P region domains on selectivity filter properties in voltage-gated K+ channels

The selectivity filter in voltage-gated K+ channels is formed at the interface of the pore loops (S5-S6 loop) from four channel subunits. Whereas most K+ channels are essentially impermeable to Na+, the Kv2.1 K+ channel conducts Na+ relatively well in the absence of K+ and selects for K+ over Na+ at least partially by an affinity-based competition mechanism. To examine whether the ability of Kv2.1 to conduct Na+ reflected unique properties of either its S5-S6 loop or channel domains that held the S5-S6 loop in place (the scaffolding), we studied chimeras made from Kv1.3 (which is completely impermeable to Na+) and Kv2.1. Chimeras that contained either the S5-S6 loop from Kv1.3 inserted into the Kv2.1 scaffolding or vice versa both made highly selective K+ channels that conducted Na+ and displayed competition between Na+ and K+ for conduction through the pore: In channels that contained the S5-S6 loop from Kv2.1, concentration-dependent block of Na+ current by either external or internal K+ differed depending on whether Kv2.1 or Kv1.3 donated the scaffolding. These results indicate that neither the S5-S6 loop nor the scaffolding from Kv2.1 possess unique attributes that permit Na+ to conduct through the channel. Furthermore, these results indicate that the competitive interaction between K+ and Na+ at the selectivity filter is determined not only by the S5-S6 loop but also by the scaffolding that holds the S5-S6 loop.     

Comparison of the pharmacological properties of rat Na(V)1.8 with rat Na(V)1.2a and human Na(V)1.5 voltage-gated sodium channel subtypes using a membrane potential sensitive dye and FLIPR

A novel, membrane potential sensitive dye and a fluorescence imaging plate reader (FLIPR) have been used to characterize the pharmacological properties of rat Na(v)1.8 voltage-gated sodium channels (VGSC) in parallel with rat Na(v)1.2a and human Na(v)1.5 VGSC subtypes, respectively. The sensitivity of recombinant Na(v)1.2a-CHO, Na(v)1.5-293-EBNA, and Na(v)1.8-F-11 cells to VGSC activators was subtype dependent. Veratridine evoked depolarization of Na(v)1.2a-CHO and Na(v)1.5-293-EBNA cells with pEC(50) values of 4.78 +/- 0.13 and 4.84 +/- 0.12, respectively (n = 3), but had negligible effect on Na(v)1.8-F-11 cells (pEC(50) < 4.5). Type I pyrethroids were without significant effect at all subtypes. In contrast, the type II pyrethroids deltamethrin and fenvalerate evoked direct depolarization of Na(v)1.8-F-11 and Na(v)1.5-293-EBNA cells. Deltamethrin potentiated the veratridine-evoked response in Na(v)1.8-F-11 cells by > or =20-fold, in contrast to a 相似文献   

Structural and functional characterization of Kv6.2 a new gamma-subunit of voltage-gated potassium channel.

We have cloned and functionally expressed Kv6.2, a new member of the Kv6 subfamily of voltage-gated potassium channel subunits. The human Kv6.2 (KCNF2) gene was mapped at 18q22-18q23. Kv6.2 mRNA is preferentially expressed in rat and human myocard. Rat and human Kv6.2 subunits appear to be unable to form functional Kv channels in a heterologous expression system, but, when coexpressed with Kv2.1 alpha subunits, heteromultimeric Kv channels were formed mediating voltage-activated delayed-rectifier type outward currents. Their kinetics and conductance-voltage relationship were different from those mediated by homomultimeric Kv2.1 channels. Yeast two-hybrid reporter assays indicated that Kv6.2 amino-termini are able to interact specifically with the Kv2.1 amino-terminus. It is proposed that this protein protein interaction underlies Kv2.1/Kv6.2 subunit assembly and the expression of functional heteromultimeric Kv2.1/Kv6.2 channels. The most resiliant feature of the Kv2.1/Kv6.2 channels was their submicromolar sensitivity to the antiarrhythmic drug propafenone. The data suggest that delayed-rectifier type channels containing Kv6.2 subunits may contribute to cardiac action potential repolarization.     

Cloning and expression of a jellyfish calcium channel beta subunit reveal functional conservation of the alpha1-beta interaction.

In high voltage-activated calcium channels, the binding between the pore-forming alpha1 subunit and the modulatory beta subunit is mediated by interaction domains in each molecule that are highly conserved among most known subunits. However, the interaction domain within CyCaalpha1, an alpha1 subunit cloned from the jellyfish Cyanea capillata, matches the canonical sequence of the alpha1 interaction domain at only four of nine sites. We have now cloned a cDNA from Cyanea neuromuscular tissue that encodes a Ca2+ channel beta subunit. The subunit, named CyCabeta, shares 47-54% identity with vertebrate beta subunit isoforms, but is most highly conserved within its interaction domain. Coexpression of CyCabeta with CyCaalpha1 in Xenopus oocytes increases the amplitude of the CyCaalpha1 current and shifts its activation to more hyperpolarized potentials. These responses are mimicked by coexpression of the rat beta2a subunit, demonstrating that the alpha1 beta interaction is functionally conserved between cnidarians and mammals. CyCabeta also markedly accelerates the rate of recovery of CyCaalpha1 from inactivation, an action that is modestly duplicated by beta2a and may represent an additional mechanism by which beta subunit isoforms differentially modulate alpha1 subunits. These findings establish that limited conservation within the alpha1 interaction domain is sufficient to allow full modulation by a beta subunit, as well as altered regulation by different beta isoforms.     

Voltage-dependent Ca2+ channel alpha2delta auxiliary subunit: structure, function and regulation.

Voltage-dependent Ca2+ channels are heteromultimeric proteins consisting minimally of a alpha1 main subunit and auxiliary alpha2delta, and beta subunits. The alpha1 subunit forms the ion-conducting pore and contains receptor sites for ligands that modify channel activity. The auxiliary subunits appear to be necessary for the expression of the native kinetic properties of the channel. In particular, the alpha2delta complex, with the transmembrane domain-containing delta subunit arising as a result of proteolysis from the C-terminal end of a alpha2delta precursor, has shown to modify the biophysical and pharmacological properties of the alpha1 subunit in different model systems. Structure-function studies have provided insight into the molecular mechanisms through which alpha2delta exerts its actions and revealed that both allosteric modulation and cellular localization of the Ca2+ channel complex are important mechanisms for alpha2delta regulation of ionic current. Recent studies have shown that the alpha2delta subunit can also support pharmacological interactions with therapeutic agents for the treatment of neurological disorders.     

LDPC在gamma-gamma信道下的性能分析

为了提高无线光通信系统的性能,将低密度奇偶校验码作为信道编码,在已知信道状态信息的条件下,对低密度奇偶校验码(LDPC)+二进制脉冲位置调制(BPPM)系统与LDPC+开关键控(OOK)系统分别在加性高斯白噪声(AWGN)、弱湍流、中等湍流和强湍流信道中的性能进行了比较;仿真了OOK和BPPM在各个强度湍流信道下的编码增益;并对LDPC结合不同进制数的脉冲位置调制(PPM)进行了分析。结果表明,LDPC+BPPM的性能优于LDPC+OOK,且随着湍流强度的增大,前者的优势则更加明显;OOK和BPPM在AWGN、弱湍流和中等湍流信道中,编码增益都随着湍流强度的增大而增大,不同的是,OOK在中等湍流中比强湍流中的大,而BPPM则在中等湍流中的比强湍流中的小;LDPC+PPM时,从4PPM到256PPM,PPM的进制数每翻1倍,系统都有约1dB的损失。因此,在湍流信道条件下,LDPC+PPM具有较大的编码增益,且实现的复杂度较低,在无线光通信中将有一定的应用前景。     

Prioritized channel assignment in a cellular radio network

Dimensioning procedures for prioritized channel assignment in a cellular radio network are considered. Under the cutoff priority discipline, the prioritized channel assignment procedures for a single cell and multicell system are formulated as nonlinear discrete capacity allocation problems. Exact incremental algorithms which efficiently solve the proposed problems are devised. They are based on the properties of the blocking probabilities of new calls and handoff calls. Given the number of available frequency channels together with the arrival rates and the grade of service (GOS) for both types of calls in each cell, algorithm SP1 generates an optimal channel assignment which ensures priority for handoff calls. Given the arrival rates and distinct GOSs for new and handoff calls, algorithm SP2 finds the minimum number of channels required in each cell. Algorithm MP extends algorithm SP1 to a multicell system and provides the prioritized channel assignment for all calls in the system. The algorithms are very fast and are appropriate for the fair allocation of frequency channels among cells     

Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel.

MCF-7 cells express voltage-activated K+ channels. In the present study, we used the patch-clamp and RT-PCR techniques to investigate the involvement of these channels during the cell cycle progression. The outward rectifier current (IK) recorded during depolarization was almost completely suppressed by the classical K+ channel blocker tetraethylammonium (TEA) in MCF-7 cells. TEA also inhibited cell proliferation, as measured with 3H-thymidine incorporation. Moreover, profound changes were observed in both the resting membrane potential (RMP) and IK during the release from the G0/G1 phase of the cell cycle. MCF-7 cells arrested in G0/G1 were depolarized (-26.3 +/- 10 mV, n = 30) and IK-density was small (9.4 +/- 5.6 pA/pF, n = 60) compared to cells progressing in the G1 phase (RMP = -60 +/- 7.9 mV; n = 35 and IK-density = 30.2 +/- 8.5 pA/pF; n = 76). IK was highly sensitive to Mg2+, astemizole and TEA (10 mM). Extracellular perfusion of 5 mM Mg2+ dramatically slowed the activation and perfusion of 2 microM astemizole inhibited both IK (20 +/- 3%) and cell proliferation (23%). Moreover, the h-EAG mRNA expression was modulated during the cell cycle. Thus, these data suggested that h-EAG K+ channels play a role in controlling the proliferation and/or cell cycle.     

Inactivation-deficient human skeletal muscle Na+ channels (hNav1.4-L443C/A444W) in stably transfected HEK-293 cells

After transient transfection of an hNav1.4-L443C/A444W mutant clone, HEK-293 cells exhibited large inactivation-deficient Na+currents. We subsequently established a stable cell line expressing robust inactivation-deficient Na+currents. Persistent late Na+currents were far more sensitive to block by class 1 anti-arrhythmic flecainide, mexiletine, propafenone, and amiodarone at 10 microM than peak Na+currents. Such results support a hypothesis that persistent late Na+currents are in vivo targets for class 1 anti-arrhythmic drugs at their therapeutic plasma concentrations. Stably transfected HEK-293 cells expressing robust inactivation-deficient Na+currents will likely be suitable for screening novel drugs that target persistent late Na+currents selectively.     

Bacillus stearothermophilus lctB gene gives rise to functional K+ channels in Escherichia coli and in Xenopus oocytes

We have cloned a small K+ channel subunit (LctB) of the gram-positive bacterium Bacillus stearothermophilus (B. stearo.). The B. stearo. LctB protein is only 134 amino acids long. The sequence contains a typical K+ channel P-domain with a K+ channel GYGD signature sequence and two hydrophobic, possibly membrane-spanning segments M1 and M2. Unexpectedly, LctB K+ channels exhibited properties which differed markedly from the ones reported for KcsA channels of the gram-positive bacterium Streptomyces lividans. LctB channels, when expressed in E. coli, were targeted to the outer membrane and not like KcsA channels to the inner membrane. After reconstitution in black lipid membrane, LctB channels mediated K+ currents at neutral pH. They were apparently not gated by pH like KcsA channels. Also, LctB cRNA produced functional LctB channels in the Xenopus oocyte expression system in marked contrast to KcsA. The results demonstrated that heterologous expression produced functional LctB channels both in E. coli and in Xenopus oocytes. It is proposed that bacterial LctB subunits can be properly handled by the Xenopus oocyte leading to the occurrence of functional LctB K+ channels in the oocyte plasma membrane.     

认知中继网络中的信道分配方法研究

认知中继网络中,对信道进行分配可以有效地提高端到端吞吐量。对三节点认知中继网络下的信道分配进行了研究。中继节点采用解码转发协议时,提出了一种次优的分配方法,将信道按信道增益排序,然后逐个地分配中继信道。中继节点采用放大转发协议时,给出了最优的信道分配方法,提出了一种次优的信道分配方法。次优方法逐个地比较中继信道采用传统协作方式传输时的端到端吞吐量、分配为双跳信道S-R和R-D链路时的端到端吞吐量完成分配。和最优方法相比,两种次优方法以较小的性能损失换取了计算复杂度的降低。给出了数值仿真,比较了两种传输方式下的端到端吞吐量性能,验证了以上方法的有效性。通过对比仿真时间,比较了最优方法和次优方法的计算复杂度。给定信道总数,对次优方法下信道分配后的比例进行了仿真,发现待分配中继信道以1/3的比例分配为直传信道;而在放大转发下,待分配中继信道几乎不被分配为双跳信道。      

Phylogenomic analysis and evolution of the potassium channel gene family

Potassium channels govern the permeability of cells to potassium ions, thereby controlling the membrane potential. In metazoa, potassium channels are encoded by a large, diverse gene family. Previous analyses of this gene family have focused on its diversity in mammals. Here we have pursued a more comprehensive study in Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes. The investigation revealed 164 potassium channel encoding genes in C. elegans, D. melanogaster, and mammals, classified into seven conserved families, which we applied to phylogenetic analysis. The trees are discussed in relation to the assignment of orthologous relationships between genes and vertebrate genome duplication.     

Efficient coupling between annealed K+-Na+ion-exchanged channel waveguides and 10/125 single-mode fibers atλ=1.321 μm

The process of thermal annealing of K⁺-Na⁺ ion-exchanged channel waveguides has been studied with the aim of optimizing their coupling efficiency with commercial single-mode fibers at λ=1.321 μm. Waveguides obtained in soda-lime glass slides, with mask apertures ranging between 13.4 and 2.6 μm, were characterized before the annealing by combining nearfield measurements and an etching procedure. The experimental results were successfully compared with a theoretical model based on the variational principle. The refractive index distribution of K⁺-Na⁺ ion-exchanged channel waveguides supporting one or a low number of modes was given: compared to the corresponding slab case, the refractive index step Δn_o remained constant, while the waveguide depth was lower. The thermal annealing process of the channels was then performed and modeled by means of the standard diffusion theory. As a result, the channel fabrication parameters for optimum guide-fiber coupling could be predicted: 0.23-dB mode mismatch losses were measured between the optimized channel and a commercial 10/125 single-mode fiber, at λ=1.321 μm     

Prioritized channel borrowing without locking: a channel sharingstrategy for cellular communications

We previously suggested a new channel sharing method for cellular communications. The method, called channel borrowing without locking (CBWL), allows real-time borrowing of channels from adjacent cells without the need for channel locking in co-channel cells. CBWL with cut-off priority for calls that arise in the cell is presented. This scheme discourages excessive channel lending and borrowing at high traffic load and promotes a more uniform grade of service throughout the service area. An analysis using macro-states and decomposition is devised to evaluate the performance of the scheme. The results are validated by simulation     

Equalization and semi-blind channel estimation for space-time block coded signals over a frequency-selective fading channel

In this paper, we investigate the equalization and channel identification for space-time block coded signals over a frequency-selective multiple-input multiple-output (MIMO) channel. The equalization has been considered by taking into account the cyclostationarity of space-time block coded signals. The minimum mean square error (MMSE) solutions have been derived for the linear and decision feedback (DF) equalizers. The channel estimation is required for the equalization. With known symbols (as pilot symbols), MIMO channels can be estimated. In addition, due to the redundancy induced by space-time block code, it is possible to identify MIMO channels blindly using the subspace method. We consider both blind and semi-blind channel estimation for MIMO channels. It is shown that the semi-blind channel estimate has fewer estimation errors, and it results in less (bit error rate) performance degradation of the MMSE linear and DF equalizers.     

Upper bounds on capacity for a constrained Gaussian channel

A low-pass and a bandpass additive white Gaussian noise channel with a peak-power constraint imposed on otherwise arbitrary input signals are considered. Upper bounds on the capacity of such channels are derived. They are strictly less than the capacity of the channel when the peak-power constrain is removed and replaced by the average-power constraint, for which the Gaussian inputs are optimum. This provides the answer to an often-posed question: peak-power limiting in the case of bandlimited channels does reduce capacity, whereas in infinite bandwidth channels it does not, as is well known. For an ideal low-pass filter of bandwidth B, the upper bound is Blog 0.934P/(N₀B) for P/( N₀B)≫1, where P is the peak power of the input signal and N₀/2 is the double-sided power spectral density of the additive white Gaussian noise     

体外冲击波对肝细胞及其质膜Na^＋—K^—ATP酶活性的影响

体外冲击波碎石术对胆石症病人进行治疗的过程中对肝细胞的超微结构和功能有无不可逆的损伤是值得探讨的。用电镜酶细胞化学方法结合电镜Ｘ射线显微分析法对冲击波作用后肝细胞质膜Ｎａ＾＋－Ｋ＋－ＡＴＰ酶活进行检测，结果显示：施冲击波１５分钟后，肝细胞质膜Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶的活性见下降，４５分钟降至最低，随后逐渐恢复，２个月时已完全恢复接近正常对照，与相同时程肝细胞微结构变化对比，酶活性受损较早，恢复亦     

Effects of intracellular Na+/K+ ratio on histone gene expression in ascitic cells of leukemia P-388 and Ehrlich cancer

The intracellular Na+/K+ ratio was studied for its effect on histone genes expression in Ehrlich carcinoma and leukemia P-388 ascites cells. After equilibration with certain Na+/K+ ratio buffers at 0-4 degrees C the cells were treated during 1 h at 37 degrees C with ouabain added to the corresponding medium. Then total RNAs were extracted and analyzed by the reaction of blot-hybridization with histone genes cluster in plasmid p604. The maximal level of histone genes expression in leukemia P-388 cells was observed under conditions when intracellular Na+/K+ ratio corresponded to those at S-phase of the mitotic cycle. In Ehrlich carcinoma ascites cells the expression of histone genes was not dependent on the Na+/K+ ratio. A conclusion is drawn that the intracellular ratio of monovalent cations is one of the possible mechanisms which regulates the gene expression during the mitotic cycle.     

A UWB WBAN channel model based on a pseudo-dynamic measurement

In this paper, we expand the knowledge of the ultra-wideband (UWB) channel in the frequency range of 3.1?C10?GHz in close proximity of a human body. The channels under dynamic conditions due to the effect of body motions are studied through the pseudo-dynamic measurement method. Firstly, the first-order statistics of the channels, namely, amplitude distributions are investigated. Secondly, the dynamic features of the channels are also studied through the second-order statistics of the channels, namely, the good and bad channel durations as well as the LCR, which are important for a cross-layer design. Three strongest peaks capturing most of the energy of the channel are taken into account. Finally, a two-state alternating Weibull renewal process model is proposed. The model provides good usability with low complexity and can then be used to better design communication network protocols for WBANs. In addition, for the sake of designing a non-coherent receiver, the dynamic delay spread of the channel, which determines an energy collector detecting the signal energy over a time window, is investigated.     

Tree‐based channel assignment schemes for multi‐channel wireless sensor networks

Many sensor node platforms used for establishing wireless sensor networks (WSNs) can support multiple radio channels for wireless communication. Therefore, rather than using a single radio channel for whole network, multiple channels can be utilized in a sensor network simultaneously to decrease overall network interference, which may help increase the aggregate network throughput and decrease packet collisions and delays. This method, however, requires appropriate schemes to be used for assigning channels to nodes for multi‐channel communication in the network. Because data generated by sensor nodes are usually delivered to the sink node using routing trees, a tree‐based channel assignment scheme is a natural approach for assigning channels in a WSN. We present two fast tree‐based channel assignment schemes (called bottom up channel assignment and neighbor count‐based channel assignment) for multi‐channel WSNs. We also propose a new interference metric that is used by our algorithms in making decisions. We validated and evaluated our proposed schemes via extensive simulation experiments. Our simulation results show that our algorithms can decrease interference in a network, thereby increasing performance, and that our algorithms are good alternatives for static channel assignment in WSNs. Copyright © 2015 John Wiley & Sons, Ltd.