Interactions between dendrotoxin, a blocker of voltage-dependent potassium channels, and charybdotoxin, a blocker of calcium-activated potassium channels, at binding sites on neuronal membranes

Abstract

Dendrotoxin I (DpI) from black mamba venom ( Dendroaspis polylepis) has high affinity binding sites on rat brain synaptic membranes. Native DpI displaced [ 125I]-DpI binding with a K i of 1 × 10 −10 M, and over 90% of specific binding was displaceable. Charybdotoxin isolated from the Israeli scorpion venom ( Leiurus quinquestriatus hebraeus), also displaced [ 125I]-DpI binding, with a K i of approximately 3 × 10 −9 M, although the displacement curve was shallower than with native DpI. Both toxins are thought to be high affinity blockers of specific K + currents. Charybdotoxin selectively blocks some types of Ca 2+-activated K + channels, whereas dendrotoxins only block certain voltage-dependent K + channels. The interaction between the two types of toxin at the DpI binding site is unexpected and may suggest the presence of related binding sites on different K + channel proteins.