Purification and partial characterization of K+ channel blockers from the venom of Dendroaspis angusticeps.
Two polypeptides (designated DTX-A and DTX-B) were purified from crude snake venom of Dendroaspis angusticeps using gel filtration, cation exchange column chromatography and cation exchange high performance liquid chromatography, and their blocking actions of K+ channels were investigated in rat brain synaptosomes. Both DTX-A and DTX-B inhibited the voltage-dependent 42K efflux from the synaptosomes. DTX-A blocked 42K efflux of both the rapidly inactivating phase (component T) and the slowly inactivating phase (component S). The inhibitory effect of DTX-A on component T was pronounced compared with that on component S. However, DTX-B selectively blocked 42K efflux of component S. The molecular weights of DTX-A and DTX-B were estimated to be ca 10,000 by SDS-polyacrylamide gel electrophoresis. The amino acid composition of these toxins is different from that of polypeptide purified from the venom of D. angusticeps (alpha-, beta-, gamma- and delta-DTX). These results suggest that DTX-A and DTX-B are new polypeptides which block voltage-dependent K+ channels selectively, and that they are useful tools for investigating the K+ channel.
Chaki
S
S
Department of Pharmacology, Taisho Pharmaceutical Co. Ltd, Saitama, Japan.
Muramatsu
M
M
Ushiyama
Y
Y
Otomo
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010455:Peptides / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012910:Snake Venoms / Q000737:chemistry / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism
D010455:Peptides; D015221:Potassium Channels; D012910:Snake Venoms; C081705:dendrotoxin A; C081706:dendrotoxin B; D011188:Potassium