Targeting Arrhythmogenic Late Sodium Current by FHF1A-Derivative FixR in Heart Failure Cardiomyocytes - PubMed
4 hours ago
- #late sodium current
- #antiarrhythmic
- #heart failure
- Enhanced late sodium current (INa,L) contributes to proarrhythmia in heart failure (HF), with FHF family proteins and CaMKII as key modulators.
- Expression of inhibitory FHF long isoforms is reduced in human, rabbit, and mouse failing hearts, correlating with increased INa,L in both HFrEF and HFpEF.
- The FHF1A-derived peptide FixR selectively reduces pathological INa,L without affecting other major cardiac ion currents, showing potent antiarrhythmic effects in cellular models.
- FixR mitigates proarrhythmic action potential changes and delays afterdepolarizations in failing cardiomyocytes, effects paralleled by the INa,L inhibitor GS967 and CaMKII inhibitor AIP.
- In vivo delivery of FixR in transgenic mice attenuates QT prolongation and arrhythmia susceptibility, supporting its therapeutic potential in HF.