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See article by Verkerk et al. [5] (pages 30–40) in this issue. “Things should be made as simple as possible, but not any simpler” Albert Einstein The traditional classification of cardiac arrhythmias makes a distinction between focal mechanisms due to abnormal electrophysiological functioning of single cells, and propagation-related mechanisms due to abnormal conduction in the multicellular tissue [1]. Single-cell arrhythmogenecity is associated with triggered activity and after-depolarizations, which are subdivided into early (EAD) and delayed (DAD) afterdepolarizations based on their timing relative to the action potential (AP) [2]. Propagation-based arrhythmias include various types of reentry [3] and spiral-wave activity [4] that involve many interconnected cardiac cells and can occur on different spatial scales (e.g. micro- or macro-reentry). The above classification into single-cell and multicellular phenomena also reflects the commonly used reductionist experimental approach that studies cellular behavior in isolated-cell preparations, in the absence of the interactions with neighboring cells that occur in the intact myocardium. Similarly, on a smaller scale, ion-channel function is studied in membrane patches or expression systems (e.g. Xenopus oocyte), away from the complex cellular environment where they interact dynamically with other ionic processes to form the AP. Since cardiac arrhythmias occur in the intact myocardium, it is essential to develop systematic understanding of the underlying processes at increasing levels of complexity and integration from the ion channel, to the cell, to groups of interacting cells, to the multicellular tissue. Such step-by-step integration can be achieved through … *Tel.: +1-216-368-4051; fax: +1-216-368-8672

Multiple interactions determine cellular electrical processes in the multicellular tissue