| Autor: |
Gang Li, Brittany D. Brumback, Lei Huang, David M. Zhang, Tiankai Yin, Catherine E. Lipovsky, Stephanie C. Hicks, Jesus Jimenez, Patrick M. Boyle, Stacey L. Rentschler |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
JACC: Basic to Translational Science. 7:1001-1017 |
| ISSN: |
2452-302X |
| DOI: |
10.1016/j.jacbts.2022.04.007 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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