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Acute Glycogen Synthase Kinase-3 Inhibition Modulates Human Cardiac Conduction.

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.

SUBMITTER: Li G

PROVIDER: S-EPMC9626903 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Acute Glycogen Synthase Kinase-3 Inhibition Modulates Human Cardiac Conduction.

Li Gang G Brumback Brittany D BD Huang Lei L Zhang David M DM Yin Tiankai T Lipovsky Catherine E CE Hicks Stephanie C SC Jimenez Jesus J Boyle Patrick M PM Rentschler Stacey L SL

JACC. Basic to translational science 20220831 10

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 ...[more]

PMID: 36337924

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