TRICLOSAN IS A KCNQ3 POTASSIUM CHANNEL ACTIVATOR

Abstract

KCNQ channels participate in the physiology of several cell types. In neurons of the central nervous system, the primary subunits are KCNQ2, 3 and 5. Activation of these channels silence the neurons, limiting action potential duration and preventing high-frequency action potential burst. Mutation of the KCNQ genes are associated with a wide spectrum of phenotypes characterized by hyperexcitability. Activation of KCNQ channels is an attractive strategy to treat epilepsy and other hyperexcitability conditions as are the evolution of stroke and traumatic brain injury. In this work we show that triclosan, a bactericide widely used in personal care products, activates the KCNQ3 channels but not the KCNQ2. Triclosan induces a voltage shift in the activation, increases the conductance and slows the closing of the channel. The effect is independent of PIP2. The putative binding site is located in the pore region but is distinct from the binding site for retigabine. Our results indicate that triclosan is a new activator for KCNQ channels.