Myocardial calcium signaling in physiology and disease

Soojeong Kang,¹ Djamel Lebeche<sup>1,2

1</sup>Cardiovascular Research Institute, ²Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Abstract: It is now well-established that calcium (Ca²⁺) is a critical regulator of myocardial function and that abnormalities in cardiomyocyte intracellular Ca²⁺ dynamics contribute to pathophysiologic changes observed in several cardiac diseases, including cardiac hypertrophy, chronic heart failure, and ventricular tachyarrhythmias. Although Ca²⁺ plays a key role in maintaining cardiac excitation–contraction coupling, it is increasingly apparent that changes in myocardial Ca²⁺ also contribute to the regulation of normal and pathological signal transduction that controls myocyte growth, hypertrophic signaling, mitochondrial energetics, and transcriptional gene expression. Interestingly, experimental evidence suggests that these multifarious Ca²⁺-dependent responses are spatially and temporally mediated by distinct cellular Ca²⁺ pools (ie, microdomains), which are generated by diverse channels and molecular signals with widely differing timescales of activation. These concepts are discussed in this review, as well as the emerging role of microRNAs in cardiac remodeling and myocardial Ca²⁺ dynamics.

Keywords: calcium signaling, calcium microdomains, hypertrophy, heart failure, arrhythmia, microRNAs