Evolving Picture of Calcium Handling in Cardiac Disease

Over the past 15 years, several influential studies have found an association between “ion channelopathies” and many inherited and acquired cardiac diseases. These functional studies have contributed to a better understanding of the foundations of cardiac disorders arising from ion channel dysfunction and intracellular Ca ²⁺ mishandling. These advances have pointed the way to the development of drugs targeting ion channels, leading to more effective treatment for many of these disorders.

Some of the Ca ²⁺ regulators implicated in heart pathophysiology are the sarcolemmal Ca ²⁺ channels, ryanodine receptors, inositol 3-phosphate receptors, and TRPs channels, in addition to many others emerging from recent research. In addition to the key role of the sarcoplasmic reticulum and plasma sarcolemma in intracellular Ca ²⁺ handling, recent data point to important contributions from other organelles such as the nucleus and mitochondria.

A confluence of experimental evidence has established a direct link between Ca ²⁺ dysregulation and acquired cardiac diseases, including heart failure, metabolic cardiomyopathies, and diabetes. A major focus of attention is post-transcriptional modifications (eg, phosphorylation, oxidation, glycosylation, and sumoylation) that impair the function of an expanding number of proteins involved in the control of intracellular Ca ²⁺ dynamics. Furthermore, many genetic mutations have been detected in some inherited arrhythmogenic disorders. These include mutations in genes encoding functional units of ion channels and/or their transporter-associated proteins that are found in patients with no cardiac structural anomalies (i.e. catecholaminergic polymorphic ventricular tachycardia), thus facilitating diagnosis of a condition that is otherwise difficult to identify.

Given the progress in the field, the aim of this Research Topic is to compile a series of original studies and reviews that will present or discuss the most recent advances in Ca ²⁺ mishandling related to both inherited and acquired cardiac diseases. The articles will be authored by researchers who have devoted their careers to the better understanding of cardiac channelopathies and discovering new candidates for cardiac disease therapy.