Recombinant Mesobuthus eupeus Potassium channel toxin gamma-KTx 2.1

Blocks human and/or rat Kv11.1/KCNH2/ERG1, Kv11.2/KCNH6/ERG2 and Kv11.3/KCNH7/ERG3 by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry. Inhibition data are the following: hERG1 (reversible, Kd=7.7 nM, IC(50)=3.3 nM, IC(50)=11.9 nM), rERG1 (reversible, Kd=19 nM), hERG2 (reversible, Kd=77 nM), rERG2 (irreversible, Kd=4.2 nM), hERG3 (reversible, Kd=11.5 nM) and rERG3 (reversible, Kd=747 nM) potassium channels. Has also a minimal effect on rat ELK1/KCNH4 potassium channels (9% inhibition at 100 nM). Both this toxin and CnErgTx1 (AC Q86QT3) share mechanism of action and have overlapping binding sites on ERG1. The potency of these two toxins is not affected by elevating potassium ion concentration from 2 to 98 mM. In addition, at high toxin concentrations, block of ERG1 macroscopic currents by these two toxins is incomplete (88%). The blockade by this toxin is preferentially closed channel state-dependent, with a component of open, but not inactive state-dependent blockade. This toxin produces a concentration-dependent prolongation of QTc in the isolated rabbit heart (16.3% at 100 nM).