Differential impacts of arrhythmia-linked loss-of-function RyR2 mutations on Ca2+ signaling in cardiac cells

Abstract

Loss-of-function (LOF) mutations in type 2 ryanodine receptor (RyR2) have been linked to various types of arrhythmias including idiopathic ventricular fibrillation (IVF), short coupled variant of Torsades de Pointes (scTdP) and long QT syndrome (LQTS). These mutations in the heterozygous state, are supposed to develop arrhythmia via abnormal Ca2+ signaling in cardiac cells, but the detailed cellular mechanisms have not been well understood. We aimed to investigate alterations of Ca2+ signaling by four LOF RyR2s in non-cardiac HEK293 and cardiac-derived HL-1 cells.