SLC4A3-related short QT syndrome assessed in human induced pluripotent stem cell-derived cardiomyocytes: mechanisms of ventricular arrhythmia and sudden cardiac death - PubMed
8 hours ago
- #Short QT syndrome
- #SLC4A3
- #Arrhythmia
- SLC4A3-related short QT syndrome (SQTS) causes sudden cardiac death due to inherited channelopathy.
- Two novel SLC4A3 variants (p.Arg370Cys and p.Lys531Thr) linked to SQTS were studied using hiPSC-derived cardiomyocytes.
- SQTS-hiPSC-CMs showed shorter action potential duration (APD), increased arrhythmia-like events, and altered ion currents (decreased ICa-L, increased INCX).
- Intracellular pH was higher (alkaline) in mutant cells, contributing to arrhythmia vulnerability.
- Drugs like quinidine and sotalol prolonged APD and reduced arrhythmia events in SQTS-hiPSC-CMs.
- SLC4A3 mutations lead to loss-of-function, intracellular alkalinization, and enhanced INCX, causing DADs and arrhythmias.