作用于电压门控离子通道的芋螺毒素研究进展

目的芋螺毒素是一类具有独特药理活性的海洋生物毒素,能高度特异性地作用于各类电压门控和配体门控离子通道及受体,已成为药理学和神经科学研究的一种有力工具和新药开发的重要来源。本文介绍了作用于各种电压门控离子通道的芋螺毒素的研究现状及其应用情况。     

人参皂苷Rg3与离子通道受体作用的研究进展

目的对人参皂苷Rg3(ginsenoside Rg3,G-Rg3)与离子通道受体作用进行全面总结。方法根据国内外最新有关文献,依据作用的离子通道受体不同进行分类介绍。结果G-Rg3可作用于离子通道受体,通过与特定氨基酸残基的作用,影响离子通道活性,进而影响某些离子的通透性。结论为G-Rg3的药理作用研究提供参考。     

离子通道门控动力学研究进展

1　导言二十世纪五十年代初 ,Hodgkin和 Huxley以乌贼大轴突为材料作生理实验 ,用电压钳位技术证实了跨膜电位决定于细胞膜的离子通透性 ,以及神经细胞的兴奋是由膜的离子通透性变化所引起的 ,这项工作是神经生物学发展史上的里程碑 ,但当时没有回答离子是如何通过细胞膜的 ,究竟是借助于膜上载体 ,还是膜内有特殊的通道 ?二十世纪七十年代中期 ,Neher和Sakrmann使用他们发明的一种特殊的膜片钳位实验技术 (膜片钳技术 ) ,证实了细胞膜上离子通道的存在 ,阐明了单个离子通道的功能 ,Neher和 Sakrmann也因此荣获一九九一年诺贝尔医学奖。…     

电压门控钙离子通道药物研究进展

电压门控钙离子通道家族（VGCC）是细胞表面一类重要的信号转换器,它能够将膜电势转变成局部胞内钙离子瞬时变化,从而启动许多重要的生理活动,例如肌肉收缩、激素分泌、神经传递和基因表达。VGCC表达和功能的异常与高血压、心绞痛、心律失常、疼痛、癫痫和帕金森病等疾病的发生有很大关系。近年来,以VGCC为靶点的药物在临床上表现出良好的治疗效果和较小的不良反应,具有较好的应用前景。综述VGCC的结构、功能以及相关药物研究进展,以期为与VGCC相关的药物开发提供参考。     

RRLC法分离分析人参中的人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1

目的：用快速分离液相色谱法分离测定人参中人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1，的含量。方法：采用ZOBAX SB—C18柱（1．8μm，3．0mm×50mm）；流动相：乙腈（A）-水（B），梯度洗脱（0～14min，19％A；14～24min，19％A→36％A；24～26min，36％A）；流速：1．0mL·min^-1；检测波长：203nm；柱温：35℃。结果：人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1的线性范围分别为0．077～1．537μg、0.058～1．156μg和0.078～1．563μg，相关系数均为0．9999。平均加样回收率（n=6）分别为98．3％，98．7％，99．2％；RSD分别为0．9％，1．0％，0．5％。结论：本方法具有快速、准确，重复性好等特点，适合于人参的含量测定。     

人参叶中Ocotillone-型人参皂苷的分离

从人参叶中分离得到一个Ocotillone 型人参皂苷和两个已知人参皂苷 ,通过化学和理化性质鉴定方法 ,此Ocotil lone 型人参皂苷被鉴定为假人参皂苷 RT5,它是迄今为止在人参中发现的第一个Ocotillone 型人参皂苷 ,同时也讨论了其可能的生物转化途径     

人参花蕾中的新皂苷

已报道从人参（ＰａｎａｘｇｉｎｓｅｎｇＣ．Ａ．Ｍｅｙｅｒ）花蕾中分离并鉴定了９种已知皂苷〔１〕和１种新皂苷成分〔２〕，进一步研究又分离得到２种新的三萜皂苷类成分ｇｉｎｓｅｎｏｓｉｄｅ（Ⅰ）和ｇｉｎｓｅｎｏｓｉｄｅ（Ⅱ）．经鉴定这２种新皂苷为３Ｏ?..     

人参和人参皂苷的抗过敏作用

曾有研究显示,某些人参皂苷对大鼠嗜碱性白血病细胞株RBL-2H3有抗过敏作用,但尚未进行详细研究。作者研究了人参、人参皂苷及原人参萜二醇人肠道细菌代谢物20-O-β-D-吡喃葡糖基-20(S)-原人参萜二醇(K)的抗过敏作用。     

人参茎叶总皂苷中人参皂苷Re的含量分析

目的：分析人参茎叶总皂苷中人参皂苷R。的含量,为人参总皂苷的质量控制提供依据。方法：色谱柱：Diamonsil C18（4．6mm×25mm,5μm）,保护柱：DIKMAEasyGuardC18（10mm×4．6mm）,流动相：乙腈-0．5％冰醋酸水溶液,梯度洗脱,流速：1．25mL／min;EISD：漂移管温度40℃,载气压力3．5bar,放大系数为7。结果：标准曲线：C=1．191×10^-7A-0．1876,线性范围：0．038～1．14mg／mL,r=0．9993,检出限：20ng（S／N〉3）,加样回收率：96．84％～104．21％。结论：该方法前处理简单,分析准确、快速,可作为人参茎叶总皂苷中人参皂苷Re的含量分析方法。     

高效液相色谱法分析人参皂苷

高效液相色谱法分析人参皂苷刘军（保定市药品检验所保定０７１０００）王燕桓傅承光（河北大学理化分析中心保定０７１００２）人参（ＰａｎａｘｇｉｎｓｅｎｇＧ．Ａ．Ｍｅｙｅｒ）是我国珍贵的传统中药，具有滋补、强壮、抗疲劳等多方面的药理和生物活性．人参皂苷是...     

Effects of duramycin on cardiac voltage-gated ion channels

The amphipathic peptide duramycin is in clinical development for the treatment of cystic fibrosis. It is deposited in cellular membranes where it binds to phosphatidylethanolamine. Duramycin may thereby change the biophysical membrane properties and perturb the function of ion channels. If so, in heart tissue, its application carries the risk to elicit cardiac arrhythmias. In fact, premature ventricular complexes were observed in the electrocardiogram during toxicological testing in dogs. To study the arrhythmogenic potential of duramycin, we investigated its effects on currents through voltage-gated hERG potassium, sodium, and calcium channels in native cells, and using a heterologous expression system, by means of the whole-cell patch clamp technique; duramycin bath concentrations between 1 nM and 0.1 μM did not generate any effects on these currents. Concentrations ≥0.3 μM, however, reduced the amplitudes of all investigated currents. Moreover, sodium current fast inactivation kinetics was slowed in the presence of duramycin. A further rise in duramycin bath concentration (≥3.3 μM) induced a leak current consistent with pore formation. The reported effects of duramycin on ion channel function are likely to arise from a change in the biophysical properties of the membrane rather than from a specific interaction of the peptide with ion channel proteins. Under therapeutic conditions (i.e., administration via inhalation), duramycin plasma concentrations are below 0.5 nM. Thus, upon inhalation, duramycin has a large safety margin and is highly unlikely to elicit arrhythmias. Eva Zebedin, and Xaver Koenig contributed equally.     

Advantages of voltage-gated ion channels as drug targets

Many human diseases result from over- or underactivity in one or more critical physiologic systems. One of the foremost challenges in modern drug discovery is the identification and selection of cellular proteins that can be specifically targeted with therapeutic agents in order to normalize aberrant processes/systems. Suitable drug targets must be validated in the human disease state and ideally, the targeted protein will fulfill similar physiologic and pathologic functions in humans and at least one animal species so that in vivo efficacy and toxicology assays with some predictive clinical relevance may be developed. Nowadays, drug targets must also be amenable to high-throughput screening so that novel molecules, which are capable of modifying cellular protein function, can be identified in large libraries of compounds. Voltage-gated ion channels satisfy many of these requirements and, as a class, are viewed as promising drug targets. Nevertheless, despite their relevance to human disease, voltage-gated ion channels remain considerably underexploited. Therein lie some of the opportunities and advantages associated with voltage-gated ion channels as drug targets.     

Human muscle voltage-gated ion channels and hereditary disease.

Insights in the field of ion channels were made possible by the Nobel-prize-winning patch-clamp technique that enables characterization of channel function, and have greatly been inspired by associated diseases pointing to regions of functional significance. These so-called ion channelopathies have common clinical features, recurrent patterns of mutations, and almost predictable mechanisms of pathogenesis. In skeletal muscle, disorders are associated with mutations in Na+, K+, Ca2+, and Cl- channels that lead to hypoexcitability (causing periodic paralysis) and to hyperexcitabilty (causing myotonia or susceptibility to malignant hyperthermia).     

Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons

Donepezil (E2020) is a novel cholinesterase inhibitor for the treatment of Alzheimer's disease. Recent studies show that it may act on targets other than acetylcholinesterase in the brain. In the present study, the actions of donepezil on voltage-gated Na+ and K+ channels were investigated in rat dissociated hippocampal neurons. Donepezil reversibly inhibited voltage-activated Na+ current (I(Na)), delayed rectifier K+ current (I(K)) and fast transient K+ current (I(A)). The inhibition of donepezil on I(Na) was dependent on the holding potential. When neurons were held at -100, -80 and -60 mV, the IC50 value was 436+/-19, 291+/-26 and 3.8+/-0.3 microM, respectively. The drug did not affect the activation, fast inactivation of I(Na) and its recovery from fast inactivation. The inhibition of donepezil on I(K) (IC50=78+/-5 microM) was voltage-dependent, whereas that on I(A) (IC50=249+/-25 microM) was voltage-independent. Donepezil caused a significant hyperpolarizing shift of the voltage-dependence of the activation and steady-state inactivation of I(K), without affecting the kinetic properties of I(A). Due to the high concentrations used, the blocking effects of donepezil on the voltage-gated ion channels are unlikely to contribute to the clinical benefits in patients with Alzheimer's disease.     

International Union of Pharmacology. XXXIX. Compendium of voltage-gated ion channels: sodium channels

This summary article presents an overview of the molecular relationships among the voltage-gated sodium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete Compendium, including data tables for each member of the sodium channel family can be found at .     

International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels

This summary article presents an overview of the molecular relationships among the voltage-gated potassium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete Compendium, including data tables for each member of the potassium channel family can be found at http://www.iuphar-db.org/iuphar-ic/.     

International Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels

This summary article presents an overview of the molecular relationships among the voltage-gated calcium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete Compendium, including data tables for each member of the calcium channel family can be found at http://www.iuphar-db.org/iuphar-ic/.     

Structure-activity and interaction effects of 14 different pyrethroids on voltage-gated chloride ion channels.

We have proposed that since the type II pyrethroids deltamethrin and cypermethrin, but not the type I pyrethroid cismethrin act on chloride channels, this could contribute to the bimodal nature of pyrethroid poisoning syndromes. We now examine a wider range of pyrethroid structures on the activity of these calcium-independent voltage-gated maxi-chloride channels. Excised inside-out membrane patches from differentiated mouse neuroblastoma cells were used, and mean channel open probabilities calculated. For single dosing at 10 microM, bioallethrin, beta-cyfluthrin, cypermethrin, deltamethrin, and fenpropathrin were all found to significantly decrease open channel probability (p < 0.05). Bifenthrin, bioresmethrin, cispermethrin, cisresmethrin, cyfluthrin isomers 2 and 4, lambda-cyhalothrin, esfenvalerate, and tefluthrin, did not significantly alter open channel probability (p > 0.05). Since the type II pyrethroids, esfenvalerate, and lambda-cyhalothrin were ineffective, we must conclude that actions at the chloride ion channel target cannot in themselves account for the differences between the two types of poisoning syndrome. Sequential dosing with type II pyrethroids caused no further chloride ion channel closure. The type I pyrethroid cisresmethrin did however prevent a subsequent effect by the mixed type pyrethroid fenpropathrin. In contrast, the type I pyrethroid cispermethrin did not prevent a subsequent effect due to the type II pyrethroid deltamethrin. The difference in effect may be the result of differences in potency, as deltamethrin had a greater effect than fenpropathrin. It therefore appears clear that in some combinations the type I and type II pyrethroids can compete and may bind to the same chloride channel target site.     

The pharmacology of ion channels: with particular reference to voltage-gated Ca2+ channels.

Ion channels are molecular machines that serve as principal integrating and regulatory devices for the control of cellular excitability. They are also major targets for drug action. The basic aspects of ion channel structure and pharmacological control are reviewed and illustrated with specific reference to a major class of therapeutic agents and molecular tools--the clinically available Ca2+ channel antagonists.