TRICLOSAN IS A KCNQ3 POTASSIUM CHANNEL ACTIVATOR

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.

The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator

Many commonly consumed plants are used as folk medicines, often with unclear molecular mechanisms. Recent studies uncovered the ubiquitous and influential KCNQ family of voltage-gated potassium (Kv) channels as a therapeutic target for several medicinal plant compounds. Capers - immature flower buds of Capparis spinosa - have been consumed for food and medicinal purposes for millennia. Here, we show that caper extract hyperpolarizes cells expressing KCNQ1 or KCNQ2/3 Kv channels. Capers are the richest known natural source of quercetin, the most consumed dietary flavonoid. Quercetin potentiated KCNQ1/KCNE1, KCNQ2/3 and KCNQ4 currents but, unusually, not KCNQ5. Strikingly, quercetin augmented both activation and inactivation of KCNQ1, via a unique KCNQ activation mechanism involving sites atop the voltage sensor and in the pore. The findings uncover a novel potential molecular basis for therapeutic effects of quercetin-rich foods and a new chemical space for atypical modes of KCNQ channel modulation.

Effect of chronic administration of nicorandil (a potassium channel activator) on body weight of two different experimental animal species

Background: Potassium channel openers (Nicorandil being the prototype) are a distinct class of drugs, used in the management of chronic stable angina pectoris. Obesity is a frequent co-morbid condition and also a risk factor for angina pectoris. Anti-obesity drugs are used more frequently these days than ever before. Therefore, it is more likely that physician would be prescribing at least 2 or more drugs while treating such comorbid conditions. This generates a need for the development of a new drug which would work against both angina and obesity. The resultant effect would be a reduction in the cost burden, incidences of side effects and possible drug- drug interactions as compared to multidrug therapy. The purpose of this study is evaluating the chronic effect of Nicorandil (graded doses) on the body weight in 2 different species of animals i.e. rabbits and mice.Methods: In this study, 30 experimental animals of each species were selected. Pretreatment weight (Mean body weight±SEM) of each group were recorded and compared with the post-treatment values of the respective group in every week up to a period of 4 weeks. The route of administration was an intraperitoneal injection.Results: Chronic administration of nicorandil causes a significant reduction in body weight at moderate to high doses in both species of the study group. (p <0.05).Conclusions: Body weight reducing, an effect of nicorandil in animals, if established in human, could enhance its acceptability in obesity with various ischemic heart diseases including angina.