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

Abstract

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 home-ostasis 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.