The hERG channel activator, RPR260243, enhances protective <i>I</i><sub>Kr</sub> current early in the refractory period reducing arrhythmogenicity in zebrafish hearts
Yu Shi, ZhaoKai Pang, Ravichandra Venkateshappa, Marvin Gunawan, Jacob Kemp, Elson Truong, Cherlene Chang, Eric Lin, Sanam Shafaattalab, Shoaib Faizi, Kaveh Rayani, Glen F. Tibbits, Victoria E. Claydon, Tom W. Claydon
Abstract
hERG channel dysfunction causes long QT syndrome and arrhythmia. Activator compounds have been of significant interest due to their therapeutic potential. We used the whole organ zebrafish heart model to demonstrate the antiarrhythmic benefit of the hERG activator, RPR260243. The activator abbreviated APD and increased refractoriness, the combined effect of which rescued induced ventricular arrhythmia. Our findings show that the targeted slowing of hERG channel deactivation and enhancement of protective currents caused by the RPR260243 activator may provide an effective antiarrhythmic approach.