Recombinant Centruroides noxius Potassium channel toxin gamma-KTx 1.1 (ERG1)

Blocks human and rat Kv11.1/KCNH2/ERG1 and Kv11.3/KCNH7/ERG3, as well as rat (but not human) Kv11.2/KCNH6/ERG2 by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry. Inhibition data are the following: hERG1 (reversible, IC(50)~7 nM), rERG1 (reversible, Kd=6.8 nM), rERG2 (irreversible, Kd=2.8 nM), hERG3 (irreversible, Kd=4.05 nM) and rERG3 (reversible, Kd=38.1 nM) potassium channels. The toxin potency is not affected by elevating potassium ion concentration from 2 to 98 mM. This toxin only blocks channels in a closed state. At high toxin concentrations, block of Kv11.1/KCNH2/ERG1 macroscopic current is incomplete (93.5%). This suggests a kinetic mechanism model with two different states of toxin-channel binding (T+C=TC*=TC; in the TC* state, the toxin binds the channel but does not occlude the pore, whereas in the TC state the toxin binds and occludes the pore). In this model, incomplete block is explained by the relatively fast dissociation rate from the blocked channel conformation (TC) relative to the rate of conversion of the toxin-channel encounter complex (TC*) to the blocked channel conformation (TC).