UC Irvine

Here, we explore the use of KCNQ channels to screen natural products that have purported rich histories of medicinal use. We identified KCNQ5 activation by tea contributes to the reduction of hypertension observed with tea consumption. We found many of the barks used by Native Americans for a variety of medicinal uses, including alleviating hypertension and stopping spasms, also activate KCNQ5 channels and identify tannic and gallic acid as contributors to this mechanism of action. We note that kratom, which is commonly consumed to mitigate opioid withdrawal symptoms, has dose-dependent effects on KCNQ5 and modulates KCNQ2/3 activity, which could explain some of the contradictory side effects experiences with kratom consumption, though more work is necessary to identify the KCNQ5-activating compound. We observe quercetin, the most consumed bioflavonoid, activates KCNQ2/3 and has fascinating effects on the activation/inactivation of KCNQ1 via an atypical mechanism of action—opening the possibility of a new chemical space for modes of KCNQ channel modulation. Finally, we assess different treatment strategies available for a child with a de novo KCNQ2 mutation.