Differential responses of ATX-II in WT, IQM, and CW. (A) ATX-II is a site 3 toxin found in sea anemone. It can bind and stabilize the VSD in DIV in the resting conformation. (B) Example ionic current traces before and after the external application of 200 nM ATX-II. In WT, ATX-II slows down the fast inactivation kinetics as was demonstrated before. In IQM, minimal effect is observed. Around 10% increase in peak current is seen, likely due to the residual fast inactivation that is not removed. In CW, however, 200 nM ATX-II almost doubled the maximum current, an effect not seen in either WT or IQM. (C and D) GV curves for IQM and CW, respectively. The conductance is normalized to the maximum conductance after ATX-II treatment. (E and F) GV curves for IQM and CW, respectively. The conductance is normalized to the maximum conductance in each condition (with or without ATX-II). The GV curve of CW is shifted 15 mV to the left after ATX-II treatment and no significant change is observed in IQM. N = 4 for IQM and N = 5 for CW. Data plotted as Mean ± SEM. Data are fitted with a two-state model.