海葵神经毒素anemone neurotoxin海葵毒素Ap-A

产品包装规格：

种属：              Human Cells

表达系统：       Prokaryotic expression system、Eukaryotic expression system 

标签：            not have

同用名：          海葵神经毒素、anemone neurotoxin、海葵毒素、Ap-A

分子量：          5.14 KDa

纯度：             Greater than 95% as determined by Tris-Bis PAGE.

储存条件：      Lyophilized from a 0.2 μm filtered solution of 20mM Tris, 100mM NaCl, pH7.5

备注：             Always centrifuge tubes before opening.Do not mix by vortex or pipetting.
                       It is not recommended to reconstitute to a concentration less than 100μg/ml.
                       Dissolve the lyophilized protein in distilled water.
                       Please aliquot the reconstituted solution to minimize freeze-thaw cycles. 

储存时间：      Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt.
                       Reconstituted protein solution can be stored at 2-8°C for 2-7 days.
                       Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months.

运输：             The product is shipped at ambient temperature.

                       Upon receipt, store it immediately at the temperature listed below.

背景：            从海葵刺丝囊毒液中分离出的多肽类神经毒素，分子量范围为3-7kD，能阻断或延迟生物体离子通道的失活，且对于各种的离子通道有着高度的特异性和亲和性，根据其作用靶点的不同可以分为作用于钠、钾及其他离子离子通道的毒素。

已经从不同海葵物种中分离出多种毒素，研究者将来源不同的海葵毒素分为两种类型：神经毒素和溶胞素。海葵神经毒素的分子量范围为3-7kD，能阻断或延迟快钠通道的失活，从而增加了钠离子内流，使细胞内钠离子的浓度增高，延长细胞的动作电位时程。据研究，海葵毒素对哺乳动物心肌表现正性肌力作用，机制既不同于儿茶酚胺类，又不同于强心苷，不影响肾上腺素受体和ATP酶，也不是通过影响钙离子的转运分布而实现的。可能是通过Na+/Ca2+离子交换机制和继发的钙通道开放刺激内钙释放，导致细胞内的钙离子浓度增加。 

海葵神经毒素的药理研究结果显示，这类毒素专一地和钠离子通道膜蛋白3位点结合，能延迟钠通道的失活。一方面，毒素作为分子探针可用于钠通道的生物学研究；另一方面，毒素对心肌组织产生非常强的正性收缩作用，而且对实验动物的心率和血压没有影响。

在已报导的氨基酸残基数介于46～49的海葵神经毒素中（另外还有几个毒素的氨基酸残基数介于27～31，称短链神经毒素），有12个氨基酸保守。根据它们的氨基酸序列又可分为两个亚类，以Ap-A、Ap-B为代表，属第一亚类；以ShⅠ、RpⅠ为代表，属第二亚类。两个亚类之间，氨基酸序列的同源性为30%左右，而属同一个亚类的毒素蛋白，氨基酸序列之间的同源性超过60%。

  海葵神经毒素的应用价值很大。它不仅可以作为分子探针，作为研究钠离子通道的结构与功能的工具药，而且因其能增强心肌收缩作用又对心率和血压没有影响，成为研究新的抗心衰药物的热点。另外值得注意的是与癫痫的关系，癫痫是由于钠离子通道突变引起的，钠通道的状态对病情有直接的影响。许多抗癫痫的药物是钠通道的阻断剂，有的药物是作用于钠通道失活过程从而达到治疗的效果。因此，海葵神经毒素可能是一种潜在的抗癫痫药物。已有四种新的基因克隆重组海葵神经毒素Hk2a、Hk7a、Hk8a和Hk16a，它们从中国南海的Anthopleurin sp.海葵分离出来。分离的SD大鼠离体心房的收缩实验己经研究了它们在心肌方面的作用机制，证明了Hk7a使心肌收缩时间最长，Hk2a使其心肌收缩程度最强。另外，在分离的SD乳鼠急性分离的神经元上，已经研究了它们对海马神经元钠通道的影响，结果表明Hk7a对钠通道开放时间和概率的作用最明显。由于这类毒素对不同的离子通道有高度的特异性和亲和性，因此，不仅可以作为一种研究离子通道结构和功能的工具，而且有望开发成为诊断和治疗离子通道相关疾病的药理学试剂。

Polypeptide neurotoxins isolated from the nematocyse venom of sea anemone, with molecular weight ranging from 3-7kD, can block or delay the inactivation of biological ion channels, and have a high specificity and affinity for various ion channels. According to their different targets, they can be divided into toxins acting on sodium, potassium and other ion channels.

A variety of toxins have been isolated from different species of anemone, and researchers have divided the anemone toxins from different sources into two types: neurotoxins and lysins. The molecular weight range of anemone neurotoxin is 3-7kD, which can block or delay the deactivation of fast sodium channels, thereby increasing the sodium ion flow, increasing the concentration of sodium ions in cells, and prolongating the action potential duration of cells. According to studies, the positive inotropic effect of anemonitoxin on mammalian myocardium is different from catecholamines and cardiac glycosides, does not affect adrenergic receptors and ATPase, and is not achieved by affecting the transport distribution of calcium ions. It may be through Na+/Ca2+ ion exchange mechanism and secondary calcium channel opening to stimulate the release of intracellular calcium, resulting in increased intracellular calcium ion concentration.

The results of pharmacological studies on neurotoxins in Anemone show that these toxins bind specifically to the 3 site of sodium channel membrane protein and can delay the inactivation of sodium channels. On the one hand, toxins can be used as molecular probes to study the biology of sodium channels. On the other hand, the toxin produced a very strong positive contractile effect on the heart muscle tissue and had no effect on the heart rate and blood pressure of the experimental animals.

Of the reported anemone neurotoxins with amino acid residues ranging from 46 to 49 (and several other toxins with amino acid residues ranging from 27 to 31, called short-chain neurotoxins), 12 amino acids are conserved. According to their amino acid sequence, they can be divided into two subclasses, Ap-A and Ap-B as representatives, belonging to the first subclass; Represented by ShⅠ and RP-ⅰ, they belong to the second subclass. The homology of amino acid sequences between the two subclasses is about 30%, while the homology between amino acid sequences of toxin proteins belonging to the same subclass is more than 60%.

The application of anemone neurotoxin is of great value. It can not only be used as a molecular probe, as a tool to study the structure and function of sodium ion channels, but also become a hot spot in the research of new anti-heart failure drugs because it can enhance the myocardial contractility without affecting the heart rate and blood pressure. It is also worth noting the relationship with epilepsy, which is caused by mutations in sodium ion channels, and the state of sodium channels has a direct impact on the condition. Many antiepileptic drugs are sodium channel blockers, and some drugs act on the sodium channel inactivation process to achieve therapeutic effects. Thus, anemone neurotoxin may be a potential antiepileptic drug. Four new gene clones of recombinant Anemone neurotoxins Hk2a, Hk7a, Hk8a and Hk16a have been obtained from Anthopleurin sp., South China Sea. The anemones are isolated. The contractile experiment of isolated SD rat atrial has studied their mechanism of action on myocardia, and it has been proved that Hk7a causes the longest contraction of myocardia and Hk2a causes the strongest contraction of myocardia. In addition, their effects on sodium channels in hippocampal neurons have been studied in the acutely isolated neurons of SD neonatal mice, and the results show that Hk7a has the most obvious effect on the opening time and probability of sodium channels. Due to the high specificity and affinity of these toxins to different ion channels, they can be used not only as a tool to study the structure and function of ion channels, but also as a pharmacological reagent for the diagnosis and treatment of ion channel-related diseases.

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