BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch.
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 microm. 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 Ca(2+)-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 IC(50) 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 microm, 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 Ca(2+)-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.
Xu
Chen-Qi
CQ
Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Graduate School, Shanghai 200031, China.
Brône
Bert
B
Wicher
Dieter
D
Bozkurt
Ozlem
O
Lu
Wu-Yuan
WY
Huys
Isabelle
I
Han
Yu-Hong
YH
Tytgat
Jan
J
Van Kerkhove
Emmy
E
Chi
Cheng-Wu
CW
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D020128:Inhibitory Concentration 50; D007313:Insecta; D007473:Ion Channels / Q000737:chemistry; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011487:Protein Conformation; D018075:RNA, Complementary / Q000378:metabolism; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013997:Time Factors; D014982:Xenopus laevis
C490373:BKTx1 protein, Buthus martensi; D007473:Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D018075:RNA, Complementary; D012604:Scorpion Venoms