Voltage dependent L-Type calcium-channels (LTCCs) are located on the cardiomyocyte membrane and regulate cardiac contraction and rhythmicity. In human pathologies, such as heart failure (HF), decreased inward calcium current (ICa) is frequently observed. Here, we generated a mimetic peptide (MP) that targets LTCCs and restores impaired intracellular calcium homeostasis through a novel mechanism. Effective delivery of MP, fused with a cell penetrating peptide, was found to correct Ca2+ alterations in a mouse model of HF, in human cardiomyocytes derived from induced pluripotent stem-cells. These data provide a proof-of-concept supporting a therapeutic role for MP to treat human diseases related to LTCC abnormalities.
Category: heart failure biology