Targeting altered calcium physiology in the heart: translational approaches to excitation, contraction, and transcription.

Calcium (Ca) is essential for excitation-contraction coupling. At the same time, Ca is of pivotal importance as a second messenger in cardiac signal transduction, where it regulates cardiac growth and function by activation of kinases and phosphatases, ultimately driving transcriptional responses and feeding back on Ca handling proteins, a phenomenon termed excitation-transcription coupling. Cardiac Ca homeostasis thus needs to be maintained via a delicate interplay of proteins to allow physiological function and adaptation, whereas disturbed Ca-handling and Ca-dependent signaling are hallmarks of heart failure. In this review, we will discuss the most recent mechanistic findings in Ca-handling and Ca-signaling proteins in the development of cardiac pathology with a focus on translational aspects.