Cardiac Pacemaking in Health and Disease: From Genes to Function

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About this Research Topic

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Background

The cardiac conduction system (CCS) is the electrical wiring system of the heart and is made up of specialized myocytes within the sinus node, the atrioventricular node and the His-Purkinje system. The sinus node is the pacemaker of the heart and the origin of the action potential. Under physiological conditions this is then propagated through the atria, the atrioventricular node and finally to the ventricles via the His-Purkinje network. Correspondingly, dysfunction of the CCS, characterised by failure to generate or conduct the sinus node impulse, is an important cause of life threatening arrhythmias manifesting as (e.g.) bradyarrhythmias, heart block, bundle branch block and  inappropriate sinus tachycardia. CCS disease is also known to worsen outcomes in atrial fibrillation, myocardial infarction and heart failure. 

The ionic and molecular mechanisms underlying pacemaker automaticity has sparked the interest of physiologists for nearly a century. Landmark studies over the past three decades have led to current view that spontaneous cardiac pacemaking is the result of mutual entrainment of an ensemble of membrane ion channels with spontaneous Ca2+ release from the sarcoplasmic reticulum. This has continued to be a dynamic and rapidly evolving field where multiple approaches including state-of-the art imaging, genomic, transgenic and bioengineering modalities, coupled with classical in vivo and in vitro electrophysiological measurements have enabled us to gain further detailed insight into pacemaker mechanisms and their dysregulation in CCS disease. Furthermore, there is a growing tendency to translate mechanistic understanding of pacemaker function to improvement in the therapy or management of CCS.

Currently, the only treatment for bradyarrhythmias arising from CCS disease is palliative- the implantation of an electronic pacemaker. Annually, >450,000 electronic pacemakers are implanted in Europe and North-America and this contributes to a significant burden on healthcare, due in part to associated peri-operative complications and impact on quality-of-life of affected individuals.

Given this clinical importance, the editors encourage authors to submit manuscripts or up-to-date reviews on novel physiological/mechanistic concepts relating to pacemaking within the CCS and/or arrhythmias arising from CCS dysfunction.

Guest editors Pietro Mesirca, Futoshi Toyoda and Alicia D'Souza, along with the editorial team of Frontiers in Physiology welcome submission of original (basic, clinical or computational) research and short review articles on the development, functional basis or modulation of pacemaker electrophysiology in health and disease.

Keywords: heart, pacemaker tissue, ion channels, atrial arrhythmia, channelopathies

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