Regulation of Intracellular Cardiomyocyte Calcium Stores by Peptides: A New Approach to Cardiac Protection

The control of cytosolic calcium is a major determinant not only of cardiac function, but also of the capability of myocardial tissue to survive damage. Increase of diastolic calcium leads rapidly to cell injury, and may be induced by a wide range of causes. In this review we describe the major points of calcium control in cardiac myocytes, mainly in mammalian ventricle, focusing on mechanisms of intracellular calcium influx during excitation, voltage gated channels of the sarcolemma and ryanodine receptors of the sarcoplasmic reticulum (SR), and efflux during relaxation, principally the sodium/calcium exchanger in membrane and the SR calcium complex. Mitochondria also depend on calcium concentration while also participating in its control. Moreover, we will outline receptor check points and their roles in physiology and pathology. We will focus on some new aspects of potential protective mechanisms that have been recently described and that involve peptide ligands and that in the case of the Neuregulin1beta/ErbB pathway are already reaching the clinical trial relevance.