Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants

Zheng, Yueming; Zhu, Xuejing; Zhou, Pingzheng; Lan, Xi; Xu, Haiyan; Li, Min; Gao, Zhaobing

To examine HCP modulation on KCNQ1/KCNE1 complex, we co-expressed the cDNAs of KCNQ1 and KCNE1 (1:1) in CHO cells. Consistent with previous reports, the effects of KCNE1 on KCNQ1 include increase in overall current amplitude, slowing of the activation and deactivation kinetics, and removal of inactivation (Fig. 4A) . We tested HCP effects at 210 mV, which is the same potential to elicit the KCNQ1 channel. We found that in the presence of 10 mM HCP, after around 120 seconds, a large instantaneous current became evident. Finally, the outward current was potentiated around 4.4760.70 fold, which is much higher than that of the KCNQ1 (Fig. 4C ). Similar to effects on KCNQ1, HCP also slowed the deactivation of the KCNQ1/ KCNE1 complex (Fig. 4A ) and left-shifted the G-V curve (Fig. 4B) . Analysis of the dose-response curve of HCP on the KCNQ1/ KCNE1 complex revealed an EC 50 value of 4.6161.29 mM.