Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4
Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4
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DOI：
10.1074/jbc.273.12.6744
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发表时间：
1998-03-20
影响因子：
4.8
通讯作者：
Lazdunski, M
中科院分区：
文献类型：
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作者：
Diochot, S;Schweitz, H;Lazdunski, M
已知海葵毒液含有对电压敏感的Na+通道以及属于Kv 1家族的延迟整流K+通道具有活性的毒素。这份报告描述了一组新的肽从Anemonia sulcata作为Kv 3钾通道家族的一个特定成员的阻滞剂的性质。这些毒素，血液抑制物质（BDS）-I和BDS-II，是43个氨基酸长，只有两个位置不同。它们与来自海葵的其他K+通道毒素（如AsKS、AsKC、ShK或BgK）没有序列同源性。在COS转染的细胞中，Kv3.4电流被BDS-I以可逆的方式抑制，IC 50值为47 nM。这种抑制是特异性的，因为BDS-I不能阻断Kv 1、Kv 2、Kv 3和Kv 4亚家族中的其他K+通道。内向整流钾离子通道对BDS-I也不敏感。BDS-I和BDS-II在脑突触膜上具有相同的结合位点，K-0.5值分别为12和19 nM。我们观察到BDS-I和BDS-II与其他海葵Na+通道毒素如AsI、AsII和AxI具有一定的序列同源性。然而，它们对神经母细胞瘤细胞中的河豚毒素敏感性Na+通道有微弱的影响，对心脏和骨骼肌细胞中的Na+通道没有影响。BDS-I和BDS-II是迄今为止发现的快速失活Kv3.4通道的第一种特异性阻断剂。
Sea anemone venom is known to contain toxins that are active on voltage-sensitive Na+ channels, as well as on delayed rectifier K+ channels belonging to the Kv1 family. This report describes the properties of a new set of peptides from Anemonia sulcata that act as blockers of a specific member of the Kv3 potassium channel family. These toxins, blood depressing substance (BDS)-I and BDS-II, are 43 amino acids long and differ at only two positions. They share no sequence homologies with other K+ channel toxins from sea anemones, such as AsKS, AsKC, ShK, or BgK. In COS-transfected cells, the Kv3.4 current was inhibited in a reversible manner by BDS-I, with an IC50 value of 47 nM. This inhibition is specific because BDS-I failed to block other K+ channels in the Kv1, Kv2, Kv3, and Kv4 subfamilies. Inward rectifier K+ channels are also insensitive to BDS-I. BDS-I and BDS-II share the same binding site on brain synaptic membranes, with K-0.5 values of 12 and 19 nM, respectively. We observed that BDS-I and BDS-II have some sequence homologies with other sea anemone Na+ channels toxins, such as AsI, AsII, and AxI. However, they had a weak effect on tetrodotoxin-sensitive Na+ channels in neuroblastoma cells and no effect on Na+ channels in cardiac and skeletal muscle cells. BDS-I and BDS-II are the first specific blockers identified so far for the rapidly inactivating Kv3.4 channel.