The Role of Calcium Handling in Heart Failure and Heart Failure Associated Arrhythmias
Description:... Under normal, healthy conditions, the contraction of cardiac myocytes, leading to the pump function of this organ, is driven by calcium-dependent mechanisms. Entry of calcium into the myocyte during the cardiac action potential causes activation of the ryanodine receptors and release of calcium from the sarcoplasmic reticulum. This process termed calcium-induced calcium release is essential for excitation-contraction coupling and enables each action potential to be transduced into a mechanical event. Indeed, in healthy myocytes, the calcium concentration in the cytosol of is elevated approximately 10-fold from a resting level of ∼100 nM to ∼1 μM. This process is finely orchestrated by a number of key proteins, which can be specifically regulated by various pathways depending on the oxygen demand. Furthermore, the specific structure of the myocyte allows certain calcium-dependent processes to be compartmentalised, increasing the efficiency and safety of this regulation.
Heart failure is a common, costly, and life-threatening condition. In 2015, for example, it affected around 40 million people globally. In patients with heart failure, the risk of sudden cardiac death and arrhythmias increases substantially. Cellular remodelling and alterations in calcium handling, which appear to contribute to the arrhythmogenic burden in heart failure, have been extensively reported. However, a number of unanswered questions remain, and each new study - while continuing to shed light on this subject - raises additional novel questions.
This current compendium of articles covers a number of aspects and comprehensively reviews current knowledge and perspectives regarding the link between calcium handling, arrhythmias and heart failure providing at the same time insights that may lead to novel therapeutic options for the future.
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