Biphasic effects on human atrial arrhythmogenicity of L-type calcium channel mutations associated with a Brugada/Short QT overlap syndrome - insights from a multiscale simulation study.

ABSTRACT: Patients with abbreviated cardiac repolarization are at increased risk of cardiac arrhythmias including ventricular and atrial fibrillation (AF). In this computational simulation study, we investigated pro-arrhythmic effects of loss-of-function missense mutations in CACNA1C (A39V and G490R Cav1.2) identified in patients with a phenotype combining Brugada syndrome with shorter-than-normal QT intervals. Biophysically-detailed computational models of human atrial cells were modified to incorporate the functional impact of the CACNA1C encoded A39V and G490R mutations on the reduction of the maximal conductance (gCaL) of L-type calcium channels (LTCC). Varying levels of gCaL reduction were considered. Effects of deficient LTCC on atrial excitation and propagation were investigated by using cell

SUBMITTER: Xiang Y 

PROVIDER: S-EPMC12629484 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature