Cellular mechanisms of arrhythmias: from rate-dependent APD variations to heterocellular coupling

Abstract

It is well established that a variety of pathological conditions induces structural and electrical remodeling of the heart which can lead to heart failure and cardiac arrhythmias. Clinically, structural remodeling is characterized by changes in the shape, size and function of the heart. These changes are based on diverse and complex cellular reactions to injury and involve both cardiomyocytes and non-cardiomyocytes. Histopathologically, remodeling typically involves cardiomyocyte hypertrophy, activation and proliferation of fibroblast, increased extracellular matrix deposition and cell death. Functionally, structural remodeling induces mechanical dysfunction and is accompanied by an increased likelihood of occurrence of life-threatening cardiac arrhythmias (Adamson et al., 2005). The electrical remodeling is usually defined as changes related to ion channels, transporters, passive electrical properties, redistribution of the gap junctions and it involves disturbances of the initiation, conduction, and coordination of the electrical stimulus in the heart. An increase in temporal variability of repolarization has been found in different pathologies to follow the electrical remodeling of the heart. In the first part of my work I have studied heterocellular electrotonic interactions between myofibroblasts and cardiomyocytes, whereas in the second part I have focused on temporal variability of ventricular cardiomyocytes repolarization. In the appendix I have studied the mechanisms of a way to electrically elicit action potentials in single cells: “the anode break excitation”