title: Studying cardiac arrhythmias in the mouse--a reasonable model for probing mechanisms?
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.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri, USA. jnerbonne@msnotes.wustl.edu
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Nerbonne
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004195:Disease Models, Animal; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006329:Heart Conduction System / Q000502:physiology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D051662:Kv1.1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D016276:Ventricular Function
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C496946:KCNA1 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C496947:Kcna1 protein, mouse; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D051662:Kv1.1 Potassium Channel; D015761:4-Aminopyridine