Year: 2022
Type: article
Abstract: Glycogen synthase kinase 3 (GSK-3) inhibition has emerged as a potential therapeutic target for several diseases, including cancer. However, the role for GSK-3 regulation of human cardiac electrophysiology remains ill-defined. We demonstrate that SB216763, a GSK-3 inhibitor, can acutely reduce conduction velocity in human cardiac slices. Combined computational modeling and experimental approaches provided mechanistic insight into GSK-3 inhibition-mediated changes, revealing that decreased sodium-channel conductance and tissue conductivity may underlie the observed phenotypes. Our study demonstrates that GSK-3 inhibition in human myocardium alters electrophysiology and may predispose to an arrhythmogenic substrate; therefore, monitoring for adverse arrhythmogenic events could be considered.
Institutions: Washington University in St. Louis, University of Washington
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,400
Awards: Graduate Research Fellowship Program (GRFP), G3549828030, G659425685, A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION, National Research Service Award-Medical Scientist, Wnt Signaling in Cardiac Conduction and Arrhythmogenesis, Pediatric Cardiovascular and Pulmonary Research Training Program
OpenAlex ID: W4293843095