BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch
BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch
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DOI：
10.1074/jbc.m312798200
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发表时间：
2004-08-13
影响因子：
4.8
通讯作者：
Chi, CW
中科院分区：
文献类型：
--
作者：
Xu, CQ;Brône, B;Chi, CW
BmBKTx1是从亚洲蝎的毒液中分离得到的一种新型短链毒素。它由31个残基组成，在结构上与SK毒素有关。然而，当对克隆大鼠SK2通道进行测试时，即使在1mum的浓度下，它也只能部分抑制rSK2电流。为了筛选其他可能的靶点，BmBKTx1随后在离体的迁移蝗虫背侧未配对正中神经元上进行了测试，其中表达了多种离子通道。结果表明，BmBKTx1能特异性阻断电压门控Ca2+激活的K+电流（bk型）。通过检测BmBKTx1对HEK293细胞中异源表达的蟑螂（pSlo）、果蝇（dSlo）和人（hSlo） BK通道α亚基的影响，证实了这一点。BmBKTx1阻断pSlo和dSlo通道的IC50分别为82 nM和194 nM。有趣的是，BmBKTx1几乎不影响hSlo电流，即使浓度高达10 muM，这表明这种毒素可能是昆虫特有的。与大多数其他也作用于Kv1.3通道的蝎子BK阻滞剂相比，BmBKTx1不像影响其他Kv通道那样影响该通道。这些结果表明，BmBKTx1是一种新型的bk型Ca2+激活K+通道阻滞剂。作为首次报道的在果蝇Slo通道dSlo上有活性的毒素，这也将极大地促进研究BK通道在这种模式生物中的生理作用。
BmBKTx1 is a novel short chain toxin purified from the venom of the Asian scorpion Buthus martensi Karsch. It is composed of 31 residues and is structurally related to SK toxins. However, when tested on the cloned rat SK2 channel, it only partially inhibited rSK2 currents, even at a concentration of 1 muM. To screen for other possible targets, BmBKTx1 was then tested on isolated metathoracic dorsal unpaired median neurons of Locusta migratoria, in which a wide variety of ion channels are expressed. The results suggested that BmBKTx1 could specifically block voltage-gated Ca2+-activated K+ currents (BK-type). This was confirmed by testing the BmBKTx1 effect on the alpha subunits of BK channels of the cockroach (pSlo), fruit fly (dSlo), and human (hSlo), heterologously expressed in HEK293 cells. The IC50 for channel blocking by BmBKTx1 was 82 nM for pSlo and 194 nM for dSlo. Interestingly, BmBKTx1 hardly affected hSlo currents, even at concentrations as high as 10 muM, suggesting that the toxin might be insect specific. In contrast to most other scorpion BK blockers that also act on the Kv1.3 channel, BmBKTx1 did not affect this channel as well as other Kv channels. These results show that BmBKTx1 is a novel kind of blocker of BK-type Ca2+-activated K+ channels. As the first reported toxin active on the Drosophila Slo channel dSlo, it will also greatly facilitate studying the physiological role of BK channels in this model organism.