據(jù)《每日科學(xué)》報(bào)道,，科學(xué)家們研究了從蜜蜂毒液中提取出來的一種毒素,，用這種毒素設(shè)計(jì)的新療法可以緩解一些疾病的癥狀，如肌肉萎縮,、抑郁癥和老年癡呆癥,。
蜜蜂神經(jīng)毒素，作為一種天然肽毒素,，其能阻止一類離子通道,，使鉀離子得以高速和有選擇性的流出神經(jīng)。如果阻止大腦神經(jīng)中的這些通道,，使得神經(jīng)興奮間歇有度,、改善學(xué)習(xí)能力，可以用于治療癡呆癥和抑郁癥,。此外,，注射蜜蜂神經(jīng)毒素還可以改善肌萎縮癥患者的癥狀。
人們對(duì)蜜蜂神經(jīng)毒素的作用機(jī)制知之甚少,。發(fā)表在《生物化學(xué)雜志》（The Journal of Biological Chemistry）上的一篇論文中,，布里斯托爾大學(xué)和比利時(shí)列日大學(xué)的兩支團(tuán)隊(duì)合作，描述了這些KCa2鉀離子通道的結(jié)果,，這也稱為SK渠道,。
利用計(jì)算機(jī)模型和遺傳學(xué)方法，研究人員就能夠精確定位蜜蜂神經(jīng)毒素綁定的離子通道,。為了阻止離子通道,，大部份的分子離子都在外部堵塞出口。令人驚訝的是,，研究人員已經(jīng)發(fā)現(xiàn),，蜜蜂神經(jīng)毒素通過聯(lián)結(jié)遠(yuǎn)距離孔隙通道，通過“變構(gòu)”機(jī)制使毛孔的形狀發(fā)生變化,，從而得以阻止離子通道,。
這個(gè)發(fā)現(xiàn)可能加快設(shè)計(jì)新的SK阻斷劑,，它可以仿效蜜蜂神經(jīng)毒素的作用，通過SK目標(biāo)通道改善神經(jīng)和肌肉狀況,。
布里斯托爾大學(xué)的生理學(xué)與藥理學(xué)專業(yè)的尼爾瑪倫教授表示：“藥物設(shè)計(jì)取決于知道目標(biāo),。我們的發(fā)現(xiàn)提供了一種新的方法來設(shè)計(jì)一種治療劑，這在一定的條件下可以幫助治療,。”(生物谷Bioon.com)
生物谷推薦原文出處：
JBC doi: 10.1074/jbc.M110.110072
Allosteric block of K（Ca）2 channels by apamin
Cedric Lamy1, Samuel J. Goodchild2, Kate L. Weatherall2, David E. Jane2, Jean-Francois Liegeois1, Vincent Seutin1 and Neil V. Marrion2,*
1 University of Liege, Belgium;
2 University of Bristol, United Kingdom
Activation of small conductance calcium activated potassium (KCa2) channels can regulate neuronal firing and synaptic plasticity. They are characterised by their high sensitivity to the bee venom toxin apamin, but the mechanism of block is not understood. For example, apamin binds to both KCa2.2 and KCa2.3 with the same high affinity (KD ~ 5 pM for both subtypes), but requires significantly higher concentrations to block functional current (IC50s of ~100 pM and ~5 nM, respectively). This suggests that steps beyond binding are needed for channel block to occur. We have combined patch clamp and binding experiments on cell lines, with molecular modelling and mutagenesis, to gain more insight into the mechanism of action of the toxin. An outer pore histidine residue common to both subtypes was found to be critical for both binding and block by the toxin, but not for block by tetraethylammonium (TEA) ions. These data indicated that apamin blocks KCa2 channels by binding to a site distinct from that used by TEA, supported by finding that the onset of block by apamin was not affected by the presence of TEA. Structural modelling of ligand-channel interaction indicated that TEA binds deep within the channel pore, which contrasted with apamin being modelled to interact with the channel outer pore by utilizing the outer pore histidine residue. This multidisciplinary approach suggested that apamin does not behave as a classical pore blocker, but blocks using an allosteric mechanism that is consistent with observed differences between binding affinity and potency of block.
