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

Among all reported activators for KCNQ channels, HCP exhibits unique subtype selectivity. The potentiation on outward current for these homomeric KCNQ channels at 210 mV is: Q1,Q2,Q4. HCP lacks sensitivity to KCNQ3. The wellcharacterized KCNQ activator, retigabine, lacks sensitivity to KCNQ1. ztz240, another KCNQ activator that is distinct from retigabine and ZnPy, potentiates KCNQ2 and KCNQ4 but does not affect KCNQ1 and KCNQ3. Although ZnPy shows similar selectivity to HCP, i.e. potentiates all KCNQ isoforms except KCNQ3, ZnPy lacks sensitivity to the KCNQ1/KCNE1 complex expressed in heterologous system [13] . Here we show HCP exhibited more potent effects on the complex than that on the KCNQ1. The unique subtype selectivity supports HCP may potentiate KCNQ channels through a different mechanism from known activators.