A novel scorpion toxin blocking small conductance Ca2+ activated K+ channel.
Small conductance calcium activated potassium channels (SK) are crucial in the regulation of cell firing frequency in the nervous system and other tissues. In the present work, a novel SK channel blocker, designated BmSKTx1, was purified from the scorpion Buthus martensi Karsh venom. The sequence of the N-terminal 22 amino acid residues was determined by Edman degradation. Using this sequence information, the full-length cDNA and genomic gene of BmSKTx1 were cloned and sequenced. By these analyses, BmSKTx1 was found to be a peptide composed of 31 amino acid residues with three disulfide bonds. It shared little sequence homology with other known scorpion alpha-KTxs but showed close relationship with SK channel blockers in the phylogenetic tree. According to the previous nomenclature, BmSKTx1 was classified as alpha-KTx14.1. We examined the effects of BmSKTx1 on different ion channels of rat adrenal chromaffin cells (RACC) and locust dorsal unpaired median (DUM) neurons. BmSKTx1 selectively inhibited apamin-sensitive SK currents in RACC with Kd of 0.72 microM and Hill coefficient of 2.2. And it had no effect on Na+, Ca2+, Kv, and BK currents in DUM neuron, indicating that BmSKTx1 was a selective SK toxin.
Xu
Chen-Qi
CQ
Institute of Neuroscience, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
He
Lin-Lin
LL
Brône
Bert
B
Martin-Eauclaire
Marie-France
MF
Van Kerkhove
Emmy
E
Zhou
Zhuan
Z
Chi
Cheng-Wu
CW
D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin / Q000378:metabolism; D001483:Base Sequence; D001667:Binding, Competitive; D019439:Chromaffin Cells / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D017931:DNA Primers; D006110:Grasshoppers; D007457:Iodine Radioisotopes / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects; D009943:Organophosphorus Compounds; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010802:Phylogeny; D026902:Potassium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D012604:Scorpion Venoms / Q000235:genetics* / Q000378:metabolism; D012605:Scorpions / Q000737:chemistry*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D051640:Small-Conductance Calcium-Activated Potassium Channels
C043517:2-(4-isothiocyanatophenoxy)-1,3,2-dioxaphosphinene 2-oxide; D017931:DNA Primers; D007457:Iodine Radioisotopes; D009943:Organophosphorus Compounds; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin