Cardiac calcium handling on trial: targeting the failing cardiomyocyte signalosome.

Targeting abnormal calcium (Ca) handling in ventricular cardiomyocytes emerged as a new paradigm for human heart failure (HF) therapy. Cardiomyocytes come with an extensive Ca signaling toolkit consisting of various Ca transporters, Ca channels, Ca buffer, and sensor proteins. Organized into self-contained signaling modules in which Ca signaling functions within highly localized environments, the cardiac Ca signalosome delivers dynamic signals with different spatial and temporal properties that relay compartmentalized Ca oscillations into specific cellular functions. As a result, Ca governs not only the cardiomyocyte contractile cycle, but also concurrently control transcription and muscle growth, electric excitability, cell survival, and energy metabolism.