Multiple interactions determine cellular electrical processes in the multicellular tissue
Authors: Y Rudy
Journal: Cardiovascular Research (2001)

30 -40) in this be achieved through novel experimental strategies or the issue.use of computer modeling.The article by Verkerk et al. in this issue of Cardiovascular Research [5] uses an elegant experimental ''Things should be made as simple as possible, but preparation, developed in Ron Joyner's laboratory and not any simpler'' Albert Einstein used previously [6-8], to simulate electrotonic interactions between a depolarized intramural ischemic region and The traditional classification of cardiac arrhythmias surviving cells in the subepicardium or subendocardium.In makes a distinction between focal mechanisms due to this preparation, an electronic circuit represents the deabnormal electrophysiological functioning of single cells, polarized region, while a real myocyte (ventricular or and propagation-related mechanisms due to abnormal Purkinje) represents the surviving (normal) cells during conduction in the multicellular tissue [1].Single-cell acute ischemia.The myocyte and the electronic circuit are arrhythmogenecity is associated with triggered activity and coupled via a variable conductance that simulates alteraafter-depolarizations, which are subdivided into early tions in the intercellular coupling.In some of the protocols, (EAD) and delayed (DAD) afterdepolarizations based on the cells were exposed to norepinephrine to simulate their timing relative to the action potential (AP) [2].effects of catecholamine release during acute ischemia.Of Propagation-based arrhythmias include various types of course, this preparation does not represent fully the reentry [3] and spiral-wave activity [4] that involve many complex substrate of ischemic myocardium and its multiinterconnected cardiac cells and can occur on different ple electrophysiological manifestations.The strategy here spatial scales (e.g.micro-or macro-reentry).The above is to use a simplified model that permits to study selectiveclassification into single-cell and multicellular phenomena ly, in a controlled fashion, the effects of alterations in also reflects the commonly used reductionist experimental coupling between a normal region and a depolarized approach that studies cellular behavior in isolated-cell ('ischemic') region with different levels of membrane preparations, in the absence of the interactions with depolarization.Such processes occur during the late phase neighboring cells that occur in the intact myocardium.(phase 1-b) of arrhythmias associated with acute ischemia Similarly, on a smaller scale, ion-channel function is (the period between 12 and 30 min following ischemia studied in membrane patches or expression systems (e.g.onset) [9].Results demonstrate the importance of elec-Xenopus oocyte), away from the complex cellular environ-trotonic influences from the depolarized region in dement where they interact dynamically with other ionic termining the behavior of the normal cell.For a critical processes to form the AP.Since cardiac arrhythmias occur range of reduced coupling, arrhythmogenic afterdepolariin the intact myocardium, it is essential to develop zations form in the normal cell, suggesting a possible role systematic understanding of the underlying processes at for triggered activity in phase 1-b arrhythmias.increasing levels of complexity and integration from the While the study provides specific insights on arion channel, to the cell, to groups of interacting cells, to rhythmogenecity during acute ischemia, it helps to illusthe multicellular tissue.Such step-by-step integration can trate a more general principle that the behavior of each building-block of the system (ion-channel, single cell) is modulated strongly by interactions with other components