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一种作用于钠离子通道的单克隆免疫毒素,其特性与蝎毒素相似。

A monoclonal immunotoxin acting on the Na+ channel, with properties similar to those of a scorpion toxin.

作者信息

Barhanin J, Meiri H, Romey G, Pauron D, Lazdunski M

出版信息

Proc Natl Acad Sci U S A. 1985 Mar;82(6):1842-6. doi: 10.1073/pnas.82.6.1842.

DOI:10.1073/pnas.82.6.1842
PMID:2580299
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC397369/
Abstract

We describe the properties of a monoclonal antibody against the Na+ channel. The antibody, 72.38, competitively inhibited (Ki = 1.5 X 10(-9) M) the binding of an 125I-labeled toxin from the Brazilian scorpion Tityus serrulatus (125I-TiTX gamma) to Na+ channels of rat brain membranes. No significant inhibition of binding of a number of other Na+ channel toxins was observed. The inhibition of 125I-TiTX gamma binding also was observed with the solubilized Na+ channel from rat brain membranes (Ki = 2 X 10(-9) M). Antibody 72.38 antagonized 125I-TiTX gamma binding to Na+ channels from different animal species (fish, avian, and mammalian) and from different tissues (electroplax, brain, heart, and muscle). Moreover, 72.38 has been used for immunofluorescence labeling of Na+ channels in rat sciatic nodes of Ranvier and cultured dorsal root ganglion cells. Electrophysiological experiments on rat muscle cells fully confirmed the similarity between TiTX gamma and 72.38 seen in binding experiments. Both produce slow oscillations of the membrane potential accompanied by bursts of action potentials which are due to a selective action on the Na+ channel. TiTX gamma and 72.38 are without effect on the ion selectivity of the Na+ channel, but they both drastically change the voltage-dependence of activation and inactivation of the Na+ channel.

摘要

我们描述了一种抗钠离子通道单克隆抗体的特性。该抗体72.38能竞争性抑制(Ki = 1.5×10⁻⁹ M)来自巴西蝎子锯齿脂鲤(125I-TiTXγ)的125I标记毒素与大鼠脑膜钠离子通道的结合。未观察到对其他多种钠离子通道毒素结合的显著抑制作用。在大鼠脑膜溶解的钠离子通道中也观察到了对125I-TiTXγ结合的抑制作用(Ki = 2×10⁻⁹ M)。抗体72.38能拮抗125I-TiTXγ与不同动物物种(鱼类、禽类和哺乳动物)以及不同组织(电鳐、脑、心脏和肌肉)的钠离子通道的结合。此外,72.38已用于大鼠坐骨神经郎飞结和培养的背根神经节细胞中钠离子通道的免疫荧光标记。对大鼠肌肉细胞的电生理实验充分证实了在结合实验中所见的TiTXγ和72.38之间的相似性。两者都会产生膜电位的缓慢振荡,并伴有动作电位的爆发,这是由于对钠离子通道的选择性作用所致。TiTXγ和72.38对钠离子通道的离子选择性没有影响,但它们都极大地改变了钠离子通道激活和失活的电压依赖性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/3835666a4e92/pnas00346-0280-h.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/dcaf3d3c7a55/pnas00346-0280-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/d532ba693407/pnas00346-0280-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/abee09cd39f7/pnas00346-0280-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/fa2f3ae73206/pnas00346-0280-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/9bc9ce7827d6/pnas00346-0280-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/7e7a70066fca/pnas00346-0280-f.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/c0ffdbdc0494/pnas00346-0280-g.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/3835666a4e92/pnas00346-0280-h.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/dcaf3d3c7a55/pnas00346-0280-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/d532ba693407/pnas00346-0280-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/abee09cd39f7/pnas00346-0280-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/fa2f3ae73206/pnas00346-0280-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/9bc9ce7827d6/pnas00346-0280-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/7e7a70066fca/pnas00346-0280-f.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/c0ffdbdc0494/pnas00346-0280-g.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6e/397369/3835666a4e92/pnas00346-0280-h.jpg

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本文引用的文献

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Isolation and characterization of toxic proteins from the venom of the Brazilian scorpion Tityus serrulatus.
Toxicon. 1983;21(2):265-77. doi: 10.1016/0041-0101(83)90011-9.
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The Ca2+-dependent slow K+ conductance in cultured rat muscle cells: characterization with apamin.培养的大鼠肌肉细胞中钙依赖的慢钾电导:蜂毒明肽的特性研究
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Reconstitution of highly purified saxitoxin-sensitive Na+-channels into planar lipid bilayers.将高度纯化的对石房蛤毒素敏感的钠离子通道重组到平面脂双层中。
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Toxin gamma of the scorpion Tityus serrulatus modifies both activation and inactivation of sodium permeability of nerve membrane.锯齿蝎毒素γ可改变神经膜钠通透性的激活和失活过程。
Pflugers Arch. 1986 Jul;407(1):92-9. doi: 10.1007/BF00580727.
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Neuronal cell adhesion molecules and cytotactin are colocalized at the node of Ranvier.神经元细胞黏附分子和细胞趋触蛋白共定位于郎飞结。
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The complete amino acid sequence of toxin TsTX-VI isolated from the venom of the scorpion Tityus serrulatus.从锯尾蝎毒液中分离出的毒素TsTX-VI的完整氨基酸序列。
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Monoclonal antibodies detect the conservation of muscarinic cholinergic receptor structure from Drosophila to human brain and detect possible structural homology with alpha 1-adrenergic receptors.单克隆抗体检测到从果蝇到人类大脑毒蕈碱胆碱能受体结构的保守性,并检测到与α1 -肾上腺素能受体可能的结构同源性。
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The sodium channel from rat brain. Purification and subunit composition.大鼠脑钠通道。纯化及亚基组成。
J Biol Chem. 1984 Feb 10;259(3):1667-75.
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Electrophysiological characterization, solubilization and purification of the Tityus gamma toxin receptor associated with the gating component of the Na+ channel from rat brain.与大鼠脑钠通道门控成分相关的蒂氏γ毒素受体的电生理特性、溶解及纯化
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Mapping the molecular structure of the voltage-dependent sodium channel. Distances between the tetrodotoxin and Leiurus quinquestriatus quinquestriatus scorpion toxin receptors.绘制电压依赖性钠通道的分子结构。河豚毒素与以色列金蝎蝎毒素受体之间的距离。
J Biol Chem. 1983 Oct 10;258(19):11958-67.
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Purification of binding protein for Tityus gamma toxin identified with the gating component of the voltage-sensitive Na+ channel.用电压敏感性Na+通道的门控成分鉴定的巴西游走蛛γ毒素结合蛋白的纯化。
Proc Natl Acad Sci U S A. 1983 Jul;80(13):4164-8. doi: 10.1073/pnas.80.13.4164.
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Protein components of the purified sodium channel from rat skeletal muscle sarcolemma.来自大鼠骨骼肌肌膜的纯化钠通道的蛋白质成分。
J Neurochem. 1983 May;40(5):1377-85. doi: 10.1111/j.1471-4159.1983.tb13580.x.
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