Abstract
Iron, the most abundant transition metal element in the human body, plays an essential role in many physiological processes. However, without a physiologically active excretory pathway, iron is subject to strict homeostatic processes acting upon its absorption, storage, mobilization, and utilization. These intricate controls are perturbed in primary and secondary hemochromatoses, leading to a deposition of excess iron in multiple vital organs including the heart. Iron overload cardiomyopathy is the leading cause of mortality in patients with iron overload conditions. Apart from mechanical deterioration of the siderotic myocardium, arrhythmias reportedly contribute to a substantial portion of cardiac death associated with iron overload. Despite this significant impact, the cellular mechanisms of electrical disturbances in an iron-overloaded heart are still incompletely characterized. This review article focuses on cellular electrophysiological studies that directly investigate the effects of iron overload on the function of cardiac ion channels, including trans-sarcolemmal and sarcoplasmic reticulum Ca2+ fluxes, as well as cardiac action potential morphology. Our ultimate aim is to provide a comprehensive summary of the currently available information that will encourage and facilitate further mechanistic elucidation of iron-induced pathoelectrophysiological changes in the heart.
Highlights
Iron is an essential metal element that serves many physiological functions
Since there is no physiologically specialized excretory pathway for iron, the total body iron content and its distribution is tightly regulated by elaborate homeostatic mechanisms acting upon iron acquisition via the gastrointestinal tract and iron recycling by the reticuloendothelial system (Crielaard et al, 2017)
Primary and secondary hemochromatoses are diseases of systemic iron mishandling, which culminate in iron overload and dysfunction of iron-laden organs (Fleming and Ponka, 2012)
Summary
Iron is an essential metal element that serves many physiological functions. These range from oxygen transport by hemoglobin to catalytic activities by various iron-containing enzymes. Requirement of iron for life can be illustrated by the ability of the immune system to restrict microbial invasion by iron-sequestrating strategies (Ganz and Nemeth, 2015). Primary and secondary hemochromatoses are diseases of systemic iron mishandling, which culminate in iron overload and dysfunction of iron-laden organs (Fleming and Ponka, 2012). Worldwide impact of this condition can be exemplified by complications of thalassemia, one of the most common monogenic disorders with the reported incidence exceeding 68,000 cases/year
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