Stress-Induced Down-Regulation of CPEB4 Disrupts Sodium Channel Regulation and Myocardial Excitability
Unstable ion channel mRNAs contribute to electrical remodeling and arrhythmic risk in heart failure. CPEB4 promotes cytoplasmic polyadenylation and stabilizes target mRNAs, thereby supporting translation. CPEB4 expression was reduced in human heart failure and in mouse and cellular models of ischemic or hypoxic stress. Cpeb4 deficiency in mice caused QRS widening, reduced R-wave amplitude, and decreased SCN5A mRNA, Na<sub>v</sub>1.5 protein, and sodium current. Restoring Cpeb4 expression after infarction preserved SCN5A/Na<sub>v</sub>1.5 and sodium current. The CPEB4-SCN5A axis is a key determinant of myocardial excitability under stress, and RNA stability may be targeted therapeutically to maintain electrical integrity in ischemic cardiomyopathy.
Authors
- Samuel C. Dudley (ORCID: https://orcid.org/0000-0001-5843-5961)
- An Xie (ORCID: https://orcid.org/0000-0002-8806-1662)
- Eunji Kim
- Gyeoung-Jin Kang
- Hong Liu
Institutions
- Minneapolis Heart Institute Foundation (US)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2026-03-16
- DOI
- https://doi.org/10.1016/j.jacbts.2026.101514
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 0.00