Implications of ion channel diversity to ventricular repolarization and arrhythmogenesis: insights from high...

Recent evidence from experiments in isolated cells suggests that substantial ion channel diversity exists throughout the heart. However, due to limitations of conventional electrophysiological recording techniques, the influence of ion channel diversity on ventricular repolarization and arrhythmia vulnerability at the level of the intact heart are poorly understood. High resolution optical mapping with voltage-sensitive dye was used to measure significant heterogeneity in the kinetics of cellular repolarization between cells across the epicardial surface (1 x 1 cm) of the intact guinea-pig heart. Such diversity of repolarization kinetics modulates dispersion of repolarization in a biphasic fashion as premature coupling interval is shortened. Moreover, evidence is provided that modulation of repolarization by a premature stimulus in a coupling interval-dependent manner also modulates arrhythmia vulnerability in parallel, ie, 'modulated dispersion' hypothesis. Therefore, due to diversity of repolarization kinetics between epicardial cells, a premature stimulus serves not only as a 'trigger' of arrhythmias, but also importantly modulates spatial dispersion of repolarization and the arrhythmogenic substrate for reentry.