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.