病毒离子通道——一种新的抗病毒靶

病毒离子通道蛋白是一种在病毒生命周期中起多种作用的小跨膜蛋白,可在宿主细胞膜上形成选择性离子通道,一些离子通道阻滞剂能阻滞这些离子通道,从而抑制这些病毒的繁殖,因而病毒离子通道蛋白可作为新的抗病毒作用靶.     

离子通道亚型与其基因共表达的关联研究

离子通道亚型与其基因共表达的关联对研究离子通道功能有重要意义。文章采用主成分分析和模糊C-均值聚类算法对数据进行分析, 将方法应用到人类和小鼠两套表达谱数据, 结果发现离子通道亚型中钾离子通道、钙离子通道、氯离子通道和受体激活型离子通道的表达谱聚类结果与生物学分类有较好的一致性, 体现了离子通道亚型在mRNA水平上的共表达, 并证实了通过离子通道表达谱能很好的对离子通道的功能亚型进行分类。     

一个改进的马尔科夫模型

离子通道是细胞膜里的大分子孔道,是跨越细胞膜里的蛋白质大分子,是神经、肌肉等细胞膜兴奋性的基础。人体细胞均具有完成特殊功能的离子通道,构建离子通道,尤其其门控行为的动力学模型,对于研究离子通道的相关课题具有重要意义。离子通道的开关反映了蛋白质构象变化的动力学过程。本文介绍了细胞膜离子通道的基本内容和几种常用模型,并根据Markov链对离子通道门控行为的一个二态（闭、开）模型的Markov过程进行了改进,得到了包含失活状态的离子通道门控行为的Markov模型。     

离子通道病研究的现状和展望

离子通道 (ionchannels)在细胞分子水平对维持机体的正常生理功能至关重要。当离子通道由于某些先天性的或后天获得性的原因导致其结构和 (或 )功能发生改变时 ,其所承载的功能必将发生异常 ,从而可能导致离子通道病 (channelopathy)的发生。作为近年新兴的一门交叉型前沿学科 ,目前离子通道病的研究模型和方法日渐完善 ,对于离子通道病的研究不仅为这类疾病的早期诊断和治疗提供了基础 ,并且将有助于对某些离子通道功能的进一步认识和了解     

离子通道对间充质干细胞增殖、骨向分化的作用

间充质干细胞(mesenchymal stem cells,MSCs)是一类具有向中胚层多向分化的干细胞,其细胞表面的离子通道表达多样,功能复杂。近年来,离子通道对间充质干细胞的功能调节备受关注。越来越多研究发现离子通道参与各种信号传递,调控细胞功能,如增殖、分化等基因的表达等。本文主要从离子通道表达的角度介绍离子通道在间充质干细胞的增殖、骨向分化中的作用。     

离子通道对胰岛β细胞中胰岛素分泌的调控作用

胰岛β细胞是胰岛细胞的一种,属于内分泌细胞,主要的生理功能是分泌胰岛素以应对葡萄糖水平的升高,其在维持葡萄糖稳态中起着重要作用。研究表明,胰岛素分泌受到多种机制的调控,其中包括多种离子通道。近年来,国内外学者越来越关注离子通道调控胰岛素分泌的过程。本文主要就钠离子通道、钾离子通道、钙离子通道以及3种离子通道之间的相互作用对胰岛素分泌的调控进行简述,同时,简单介绍了离子通道抑制剂在糖尿病临床中的应用,并展望了离子通道研究在未来糖尿病治疗方面的潜在应用价值。     

结核分枝杆菌感染对人巨噬细胞离子通道及其调控元件转录表达的影响

为研究人巨噬细胞的离子通道及其调控元件是否参与了抗结核分枝杆菌感染免疫,利用表达谱芯片技术研究细菌感染后主巨噬细胞基因的表达情况,在全局表达谱分析的基础上,重点分析了离子通道及其调控元件的表达,并比较无毒株和临床分离有毒株在诱导离子通道及其调控元件表达方面的差异。结果表明,细菌感染影响离子通道及其调控元件基因的表达,涉及的离子通道包括钾通道、钠通道、氯通道、钙通道,差异表达的调控元件包括G蛋白、G蛋白偶联受体、蛋白质激酶和磷酸化酶;临床株感染影响的离子通道及其调控元件较无毒株广泛和丰富。这些观察结果提示,离子通道及其调控元件参与了宿主细胞对感染细菌的免疫应答,有关离子通道及其调控元件在抗结核免疫中的作用有待进一步研究。芯片研究的结果为将来的研究提供了线索。     

一个改进的马尔科夫模型

离子通道是细胞膜里的大分子孔道,是跨越细胞膜里的蛋白质大分子,是神经、肌肉等细胞膜兴奋性的基础.人体细胞均具有完成特殊功能的离子通道,构建离子通道,尤其其门控行为的动力学模型,对于研究离子通道的相关课题具有重要意义.离子通道的开关反映了蛋白质构象变化的动力学过程.本文介绍了细胞膜离子通道的基本内容和几种常用模型,并根据Markov链对离子通道门控行为的一个二态(闭、开)模型的Markov过程进行了改进,得到了包含失活状态的离子通道门控行为的Markov模型.     

离子通道在免疫细胞和免疫应答反应中的功能研究进展

离子通道是一类介导各种无机离子通过疏水性细胞脂膜的膜蛋白,它们广泛分布在各种细胞和组织中,通过调节细胞内外的离子浓度参与细胞膜电位建立并在各种生理活动中行使功能,其结构和功能正常是维持生命过程的基础。分子克隆、蛋白结构解析和膜片钳等科学技术的快速发展推进了离子通道生物物理学研究,同时也极大地促进了离子通道与病理生理学之间关系的研究。免疫系统由免疫细胞、免疫组织和它们所分泌的免疫活性物质构成,在维护机体稳态,保护身体不受病毒、细菌和其它入侵者的干扰中发挥至关重要的作用。研究表明,离子通道在免疫细胞中大量表达并参与调节免疫反应,在免疫系统中发挥重要作用。本文综述了目前离子通道在免疫系统中的主要研究进展,包括离子通道在免疫细胞中的表达及其所参与的免疫细胞活性调节,离子通道介导离子流调控的淋巴细胞发育,以及离子通道在天然免疫应答和适应性免疫应答中的功能与作用机制。此外,本文还对目前相关研究中尚待回答的关键科学问题进行了分析与展望,以期为未来进一步探究离子通道在免疫系统中的功能提供参考。     

Ion channels and transporters in cancer. 3. Ion channels in the tumor cell-microenvironment cross talk

The traditional view of cancer as a collection of proliferating cells must be reconsidered, and cancer must be viewed as a "tissue" constituted by both transformed cells and a heterogeneous microenvironment, that tumor cells construct and remodel during multistep tumorigenesis. The "tumor microenvironment" (TM) is formed by mesenchymal, endothelial, and immune cells immersed in a network of extracellular matrix (ECM) proteins and soluble factors. The TM strongly contributes to tumor progression, through long distance, cell-to-cell or cell-to-matrix signals, which influence different aspects of tumor cell behavior. Understanding the relationships among the different components of the cancer tissue is crucial to design and develop new therapeutic strategies. Ion channels are emerging as relevant players in the cross talk between tumor cells and their TM. Ion channels are expressed on tumor cells, as well as in the different cellular components of the TM. In all these cells, ion channels are in a strategic position to sense and transmit extracellular signals into the intracellular machinery. Often, this transmission is mediated by integrin adhesion receptors, which can be functional partners of ion channels since they form molecular complexes with the channel protein in the context of the plasma membrane. The same relevant role is exerted by ion transporters, which also contribute to determine two facets of the cancer tissue: hypoxia and the acidic extracellular pH. On the whole, it is conceivable to prospect the targeting of ion channels for new therapeutic strategies aimed at better controlling the malignant progression of the cancer tissue.     

Role of ion channels in regulating Ca2+ homeostasis during the interplay between immune and cancer cells

Ion channels are abundantly expressed in both excitable and non-excitable cells, thereby regulating the Ca²⁺ influx and downstream signaling pathways of physiological processes. The immune system is specialized in the process of cancer cell recognition and elimination, and is regulated by different ion channels. In comparison with the immune cells, ion channels behave differently in cancer cells by making the tumor cells more hyperpolarized and influence cancer cell proliferation and metastasis. Therefore, ion channels comprise an important therapeutic target in anti-cancer treatment. In this review, we discuss the implication of ion channels in regulation of Ca²⁺ homeostasis during the crosstalk between immune and cancer cell as well as their role in cancer progression.     

Insights from modeling three-dimensional structures of the human potassium and sodium channels

Ion channels allow the movement of ions across cell membranes. Nearly all cells have membranes spanned by ion channels, without which human nerves simply would not work. Ion channels are formed by the aggregation of subunits into a cylindrical configuration that allows a pore, thus forming a kind of tube for ion trafficking. In the present study, the subunits of the human potassium channel are formed by four identical protein chains, whereas for the case of the human sodium channel, the corresponding subunits are actually four hetero-domains formed by the folding of a very large but single protein chain. Since both of the two ion channels are important targets for drug discovery, the 3D (dimensional) structures of their pore regions were developed. On the basis of the 3D models, some important molecular biological mechanisms were discussed that may stimulate novel strategies for therapeutic treatment of the diseases related to ion channel disorders, such as long QT syndrome and chronic pain.     

Understanding ion channel selectivity and gating and their role in cellular signalling

Ion channels play an essential role in the communication between and within cells. Here some of the different ion channel proteins and the roles they perform are introduced, before a discussion of the mechanisms by which they discriminate between different ion types and open and close to allow the passage of ions at the appropriate times.     

Ion channels and transporters regulate nutrient absorption in health and disease

Ion channels and transporters are ubiquitously expressed on cell membrane, which involve in a plethora of physiological process such as contraction, neurotransmission, secretion and so on. Ion channels and transporters is of great importance to maintaining membrane potential homeostasis, which is essential to absorption of nutrients in gastrointestinal tract. Most of nutrients are electrogenic and require ion channels and transporters to absorb. This review summarizes the latest research on the role of ion channels and transporters in regulating nutrient uptake such as K+ channels, Ca2+ channels and ion exchangers. Revealing the mechanism of ion channels and transporters associated with nutrient uptake will be helpful to provide new methods to diagnosis and find potential targets for diseases like diabetes, inflammatory bowel diseases, etc. Even though some of study still remain ambiguous and in early stage, we believe that ion channels and transporters will be novel therapeutic targets in the future.     

Role of ion channels during cell division

Ion channels are transmembrane proteins whose canonical function is the transport of ions across the plasma membrane to regulate cell membrane potential and play an essential role in neural communication, nerve conduction, and muscle contraction. However, over the last few years, non-canonical functions have been identified for many channels, having active roles in phagocytosis, invasiveness, proliferation, among others. The participation of some channels in cell proliferation has raised the question of whether they may play an active role in mitosis. There are several reports showing the participation of channels during interphase, however, the direct participation of ion channels in mitosis has received less attention. In this article, we summarize the current evidence on the participation of ion channels in mitosis. We also summarize some tools that would allow the study of ion channels and cell cycle regulatory molecules in individual cells during mitosis.     

Ionenkanäle – Einführung aus physiologischer Perspektive

Ion channels form a complex class of membrane transport proteins. They are often classified according to their selective permeability for particular ion species as well as to their gating properties, which are controlled by either membrane voltage, ligand binding or physical stimuli. Ion transport through membrane pores embedded in protein channel complexes possesses both a chemical and an electrical dimension with ion flux causing both charge separations as well as changes in ionic concentrations. This electrochemical double-nature of ion transport is reflected in the two main physiological domains of ion channel function: in excitable cells many ion channels predominately control membrane voltage to generate fast electrical signaling, while epithelial or intracellular ion channels are mainly involved in directional ion transport. Given this framework, individual channelopathies display their major deficiencies either in fast electrical signaling or ion transport itself.     

Electrophysiology of mammalian Schwann cells

Schwann cells are the satellite cell of the peripheral nervous system, and they surround axons and motor nerve terminals. The review summarises evidence for the ion channels expressed by mammalian Schwann cells, their molecular nature and known or speculated functions. In addition, the recent evidence for gap junctions and cytoplasmic diffusion pathways within the myelin and the functional consequences of a lower-resistance myelin sheath are discussed.

The main types of ion channel expressed by Schwann cells are K⁺ channels, Cl⁻ channels, Na⁺ channels and Ca²⁺ channels. Each is represented by a variety of sub-types. The molecular and biophysical characteristics of the cation channels expressed by Schwann cells are closely similar or identical to those of channels expressed in peripheral axons and elsewhere. In addition, Schwann cells express P₂X ligand-gated ion channels. Possible in vivo roles for each ion channel type are discussed. Ion channel expression in culture could have a special function in driving or controlling cell proliferation and recent evidence indicates that some Ca²⁺ channel and Kir channel expression in culture is dependent upon the presence of neurones and local electrical activity.     

结直肠离子通道与先天性巨结肠关系的研究进展

离子通道是细胞膜上一类特殊亲水性蛋白微孔道,也是肌肉、神经细胞等电活动的物质基础。目前研究通过生物学及离子通道膜片钳等新技术对离子通道有了进一步的认识,并逐步发掘离子通道的结构功能异常与疾病的发生存在的紧密关系。先天性巨结肠症(Hirschsprung's Disease,HD)又称无神经节细胞症,是小儿外科的常见疾病之一。HD临床表现为胎粪排出延迟、顽固性便秘及腹胀,常并发小肠结肠炎、低位肠梗阻等。目前研究尚未完全明确HD的发病机制,本文对HD的发生与结直肠离子通道功能间的关系作一综述。     

Electrical correlates of secretion in endocrine and exocrine cells

Many types of secretory cells including neurons and cells of endocrine and exocrine glands show changes in electrical potential and resistance when secretion is stimulated. These electrical correlates result from the movement of ions across the cell membrane through specific ion-selective channels. In neurons and certain endocrine cells (such as pancreatic beta cells and certain cells of the anterior pituitary), these channels are voltage dependent and open transiently upon depolarization leading to action potentials. Thus some endocrine cells are electrically excitable, a property previously held to occur only in nerve and muscle. In other nonexcitable endocrine and exocrine cells (such as the pancreas and parotid), ion channels are responsive to either occupancy of specific membrane receptors or changes in intracellular metabolites and second messengers. Ion fluxes through these latter channels also lead to changes in the electrical potential and resistance, but these changes are generally more sustained and action potentials are not seen. The entry of Ca2+ through both voltage-dependent and voltage-independent ion channels plays a major role in the activation of secretion via exocytosis.