The hERG channel activator, RPR260243, enhances protective IKr current early in the refractory period reducing arrhythmogenicity in zebrafish hearts

Author:

Shi Yu Patrick1,Pang ZhaoKai1,Venkateshappa Ravichandra1,Gunawan Marvin1,Kemp Jacob1,Truong Elson1,Chang Cherlene1,Lin Eric1ORCID,Shafaattalab Sanam1ORCID,Faizi Shoaib1,Rayani Kaveh1ORCID,Tibbits Glen F1,Claydon Victoria E.1,Claydon Thomas W.1

Affiliation:

1. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, British Columbia, Canada

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.

Funder

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council of Canada

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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