Studying cardiac arrhythmias in the mouse--a reasonable model for probing mechanisms? - PubMed (original) (raw)
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Studying cardiac arrhythmias in the mouse--a reasonable model for probing mechanisms?
Jeanne M Nerbonne. Trends Cardiovasc Med. 2004 Apr.
Abstract
The normal mechanical functioning of the heart depends on proper electrical functioning, reflected in the sequential activation of pacemaker cells, and the normal propagation of activity through the ventricles. Myocardial electrical activity is evident in the form of action potentials, reflecting the activation (and inactivation) of depolarizing (Na(+), Ca(2+)) and repolarizing (K(+)) current channels. There are multiple types of myocardial K(+) channels, contributing to regional differences in action potential waveforms and to the generation of normal cardiac rhythms. The conduction and propagation of activity through the myocardium depends on electrical coupling between cells, mediated by gap junction channels. In the diseased myocardium, action potential waveforms and conduction are affected markedly, owing to changes in the functional expression of repolarizing K(+) and other channels. These changes can lead to desynchronization of the heart and to arrhythmia generation. There is presently greater interest in defining the cellular, molecular, and systemic mechanisms contributing to the generation and the maintenance of cardiac arrhythmias. Although a variety of experimental (animal) model systems have been (and are being) exploited in these efforts, the mouse is being used increasingly, due to the ease with which molecular genetic strategies can be applied. The important issue is whether the mouse is an appropriate model system to explore arrhythmia mechanisms.
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