Can triggered arrhythmias arise from proagation of calcium waves 可以触发性心律失常引起的钙波的传播.docVIP

Can triggered arrhythmias arise from propagation of Ca2+ waves between cardiac cells? Amanda F. Nahhas1, Manvinder S. Kumar1, Matthew J. O’Toole1, Gary L. Aistrup1, J. Andrew Wasserstrom1 1Department of Medicine (Cardiology) and the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 TABLE OF CONTENTS 1.Abstract 2. Introduction 3. Intracellular Ca2+ cycling and arrhythmias 4. Connexins, gap junctions and cell-cell communication 5. Ca2+ spread between cardiac myocytes in culture and cell pairs 6. Ca2+ spread between myocytes in intact tissues and whole heart 7. Mechanisms and regulation of intercellular Ca2+ wave propagation 8. Intercellular Ca2+ wave propagation and triggered arrhythmias 9. References  1. ABSTRACT Intracellular Ca2+ overload can induce regenerative Ca2+ waves that activate inward current in cardiac myocytes, allowing the cell membrane to achieve threshold. The result is a triggered extrasystole that can, under the right conditions, lead to sustained triggered arrhythmias. In this review, we consider the issue of whether or not Ca2+ waves can travel between neighboring myocytes and if this intercellular Ca2+ diffusion can involve enough cells over a short enough period of time to actually induce triggered activity in the heart. This review is not intended to serve as an exhaustive review of the literature summarizing Ca2+ flux through cardiac gap junctions or of how Ca2+ waves move from cell to cell. Rather, it summarizes many of the pertinent experimental studies and considers their results in the theoretical context of whether or not the intercellular propagation of Ca2+ overload can contribute to triggered beats and arrhythmias in the intact heart. 2. INTRODUCTION Abnormal intracellular Ca2+ cycling is responsible for triggered arrhythmias, particularly in the setting of intracellular Ca2+ overload that results from ischemia, cell damage, pharmacological or neurohormonal alterations