据《每日科学》报道，科学家们研究了从蜜蜂毒液中提取出来的一种毒素，用这种毒素设计的新疗法可以缓解一些疾病的症状，如肌肉萎缩、抑郁症和老年痴呆症。
 
蜜蜂神经毒素，作为一种天然肽毒素，其能阻止一类离子通道，使钾离子得以高速和有选择性的流出神经。如果阻止大脑神经中的这些通道，使得神经兴奋间歇有度、改善学习能力，可以用于治疗痴呆症和抑郁症。此外，注射蜜蜂神经毒素还可以改善肌萎缩症患者的症状。
 
人们对蜜蜂神经毒素的作用机制知之甚少。发表在《生物化学杂志》（The Journal of Biological Chemistry）上的一篇论文中，布里斯托尔大学和比利时列日大学的两支团队合作，描述了这些KCa2钾离子通道的结果，这也称为SK渠道。
 
利用计算机模型和遗传学方法，研究人员就能够精确定位蜜蜂神经毒素绑定的离子通道。为了阻止离子通道，大部份的分子离子都在外部堵塞出口。令人惊讶的是，研究人员已经发现，蜜蜂神经毒素通过联结远距离孔隙通道，通过“变构”机制使毛孔的形状发生变化，从而得以阻止离子通道。
 
这个发现可能加快设计新的SK阻断剂，它可以仿效蜜蜂神经毒素的作用，通过SK目标通道改善神经和肌肉状况。
 
布里斯托尔大学的生理学与药理学专业的尼尔玛伦教授表示：“药物设计取决于知道目标。我们的发现提供了一种新的方法来设计一种治疗剂，这在一定的条件下可以帮助治疗。”

原文出处：

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.