Lysosomal Ca²⁺ flux modulates automaticity in ventricular cardiomyocytes and correlates with arrhythmic risk.

ABSTRACT: Automaticity involves Ca²⁺ handling at the cell membrane and sarcoplasmic reticulum (SR). Abnormal or acquired automaticity is thought to initiate ventricular arrhythmias associated with myocardial ischemia. Ca²⁺ flux from mitochondria can influence automaticity, and lysosomes also release Ca²⁺. Therefore, we tested whether lysosomal Ca²⁺ flux could influence automaticity. We studied ventricular human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), hiPSC 3D engineered heart tissues (EHTs), and ventricular cardiomyocytes isolated from infarcted mice. Preventing lysosomal Ca²⁺ cycling reduced automaticity in hiPSC-CMs. Consistent with a lysosomal role in automaticity, activating the transient receptor potential mucolipi

SUBMITTER: Xie A 

PROVIDER: S-EPMC10255768 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature