Referenced in: none

Automatically associated channels: Kv1.2

Title: Tityustoxin-K alpha, a structurally novel and highly potent K+ channel peptide toxin, interacts with the alpha-dendrotoxin binding site on the cloned Kv1.2 K+ channel.

Authors: T R Werkman, T A Gustafson, R S Rogowski, M P Blaustein, M A Rogawski

Journal, date & volume: Mol. Pharmacol., 1993 Aug , 44, 430-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8355670

Abstract
The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-K alpha (TsTX-K alpha) and Dendroaspis angusticeps (snake) toxin dendrotoxin (alpha-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, alpha-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-K alpha produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-K alpha did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-K alpha blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-K alpha the blocking potency of alpha-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. alpha-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-K alpha, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-K alpha and alpha-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites.