Characterization of the PLN-R14Del mutation in hiPSC-derived cardiomyocytes

Abstract

Phospholamban (PLN) is the natural inhibitor of the sarco/endoplasmic reticulum Ca2+ ATP-ase (SERCA2a). Heterozygous PLN-R14Del mutation is associated with an arrhythmogenic dilated cardiomyopathy (DCM), whose pathogenesis has been attributed to SERCA2a “super-inhibition”. Test in human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CM) harvested from a PLN-R14del carrier whether i) Ca2+ dynamics and protein localization were compatible with SERCA2a superinhibition and ii) functional abnormalities could be reverted by pharmacological SERCA2a activation with (PST3093).