反毒为药：精准控制河鲀毒素用作局部麻醉药的新进展

钠离子通道阻断剂河鲀毒素(TTX)是致命的毒素之一,却是极具价值的神经生物学和生理学等生命科学研究领域的工具药.近年来,越来越多的研究指出,TTX具有强大的局部麻醉潜能,有望成为替代氨基酯类和氨基酰胺类局部麻醉药、避免阿片类药物滥用的新型麻醉药物.本文综述TTX局部麻醉应用的辅助药物、TTX缓释及控释给药系统等相关研究,旨在为局部麻醉新药研发提供参考并探讨新的思路.     

A Procedure for Purification of the Ryanodine Receptor from Skeletal Muscle

In this paper, we describe a simple and reproducible method for purifying large quantities of ryanodine receptor from skeletal muscle membranes. The procedure involves the use of ion exchange chromatography and sucrose gradient centrifugation to purify the protein which has been identified as the calcium release protein of the sarcoplasmic reticulum (Imagawa, T., Smith, J., Coronado, R. and Campbell, K. (1987) J. Biol. Chem. 262:16,636–16,643). Addition of micromolar quantities of unlabeled ryanodine prior to solubilization and throughout the isolation procedure appears to stabilize the tetrameric structure of the ryanodine receptor. The purified receptor, consisting predominantly of a 400K polypeptide on SDS-PAGE, binds [³H]ryanodine with a binding affinity similar to that in membranes. Overall recovery of ryanodine binding activity was 21% of the initial activity with a 30-fold purification of the receptor.     

Effect of the exogenous soyabean phyto-oestrogen genistein on sperm quality, ATP content and fertilization rates in channel catfish Ictalurus punctatus (Rafinesque) and walleye Sander vitreus (Mitchill)

This study examined whether the soya phyto-oestrogen genistein would have an effect on spermatozoa quality and in vitro fertilization capacity in mature channel catfish Ictalurus punctatus or walleye Sander vitreus . For both species, motility time and motility rank were significantly different among treatment groups and control, with higher genistein concentrations producing significantly lower motility time and motility rank ( P ≤ 0·01). Walleye and channel catfish ATP content was significantly lower compared to control treatments at several incubation concentrations and was significantly related to fertilization rate. Fertilization rate was significantly dependant on genistein incubation concentrations ( P ≤ 0·01). Additionally, logistic regression showed a significant negative relation between genistein concentration and fertilization in channel catfish ( P ≤ 0·01). These results establish that genistein could play a role in reproductive performance within aquaculture species. In addition, these findings warrant further examination of the impact of phyto-oestrogens in broodstock feeds.     

Possible existence of ion pairs at the mouths of ion channels

An electrostatic calculation suggests that when an ion is bound near the mouth of a channel penetrating a low-dielectric membrane, a counter ion may form an ion pair with this ion. The tendency towards ion-pair formation is remarkably enhanced at channel mouths by forces (image forces) arising from the charges induced on the boundaries between different dielectrics. The binding constant for the formation of ion-pairs of monovalent ions is estimated under the assumption that local interactions between the counter ion and the channel wall are negligibly small. It is of the order of 1–10 molal^?1 or more for the binding of a Cl^? (F^?) counter ion to an $\text{Na}{}^{\mathrm{+}}$ ($\text{Li}{}^{\mathrm{+}}$) ion if appropriate conditions are fulfilled. The binding constant depends on the position of the binding site, the dimensions and geometries of the channel and channel mouth, and the state of ion loading of the channel, as well as the ionic species. The present results also indicate that when cation (anion) channels have anionic (cationic) groups as integrant parts of their channel walls, interactions between these charged groups and permeant ions are markedly enhanced by the image forces.     

A Putative Calcium-Permeable Cyclic Nucleotide-Gated Channel, CNGC18, Regulates Polarized Pollen Tube Growth

A tip-focused Ca^2＋ gradient is tightly coupled to polarized pollen tube growth, and tip-localized influxes of extracellular Ca^2＋ are required for this process. However the molecular identity and regulation of the potential Ca^2＋ channels remains elusive. The present study has implicated CNGC18 （cyclic nucleotide-gated channel 18） in polarized pollen tube growth, because its overexpression induced wider and shorter pollen tubes. Moreover, CNGC18 overexpression induced depolarization of pollen tube growth was suppressed by lower extracellular calcium （[Ca^2＋]ex）. CNGC18-yellow fluorescence protein （YFP） was preferentially localized to the apparent post-Golgi vesicles and the plasma membrane （PM） in the apex of pollen tubes. The PM localization was affected by tip-localized ROP1 signaling. Expression of wild type ROP1 or an active form of ROP1 enhanced CNGC18-YFP localization to the apical region of the PM, whereas expression of RopGAP1 （a ROP1 deactivator） blocked the PM localization. These results support a role for PM-Iocalized CNGC18 in the regulation of polarized pollen tube growth through its potential function in the modulation of calcium influxes.     

昆虫击倒抗性基因突变对钠通道功能的影响

该文综述了昆虫钠通道基因的表达与功能特性、击倒抗性突变的功能和这些突变对钠通道门控的影响,以及钠通道基因突变与抗性表现型之间的因果关系;还讨论了这些突变增强击倒抗性的分子机理。     

KcsA通道对Na+、K+及Rb+离子选择性的统计热力学研究

钾离了的通透率至少比钠离子的通透率大10000倍,这个问题至今没有很好地解决,为了存分子水平阐释钾离子通道的选择性机制,以KcsA钾通道X射线衍射结构为基础,采用密度泛函理论计算了不同离子在离子通道中的位能．计算结果表明,Rb^ 离子具有与K^ 离子相类似的位能曲线,但是其在通透过程遇到的位垒要比K^ 离子的位垒高,因而所对应的通透率也就小十钾离子的通透率,而钠离子的的通透率仅仅足钾离子通透率的0．0067％．文中所涉及的系统仪仅包含269个原子,而用分子动力学虽然也可以得到相近的结果,但是它的系统火小为41000个原子．     

KATP通道基因在大鼠组织中的表达

为检测大鼠肺动脉平滑肌及支气管平滑肌中KATP．通道亚基的表达情况,应用RT-PCR技术．从原代培养的Wistar大鼠肺动脉平滑肌及支气管平滑肌细胞第3—5代提取总RNA,逆转录．并进行PCR扩增鉴定．发现肺动脉平滑肌细胞有Kir6.1、SUR1和SUR2B的表达,其中SUR1表达量较弱,支气管平滑肌细胞有Kir6.1和SUR2B的表达。     

KCNQ1基因及其编码钾通道的研究概况

本文介绍了KCNQ1基因和其编码的通道蛋白的结构、生理学功能及电生理特点。归纳了围绕KCNQ1基因的热点研究方向和成果,并展望了未来的研究趋势。对基础医学上关心的KCNQ1基因突变与疾病的关系,及相关的病理药理学研究做了较为详细的介绍。