Circulation Research. 2001;89:944-956
doi: 10.1161/hh2301.100349
doi: 10.1161/hh2301.100349
© 2001 American Heart Association, Inc.
Reviews |
Genetic Manipulation of Cardiac K+ Channel Function in Mice
What Have We Learned, and Where Do We Go From Here?
From the Departments of Molecular Biology and Pharmacology (J.M.N.) and Cell Biology and Physiology (C.G.N.), Washington University Medical School, St Louis, Mo; the Division of Neuroscience (T.L.S.), Children’s Hospital and Harvard Medical School, Boston, Mass; and INSERM U533 (D.E.), Hôpital Hotel-Dieu, Nantes, France.
Correspondence to Denis Escande, Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moléculaires, INSERM U533, 1 rue Gaston Veil, Faculté de Médecine, 44035 Nantes, France. E-mail denis.escande{at}nantes.inserm.fr
Abstract
In the mammalian myocardium, potassium (K+) channels control resting potentials, action potential waveforms, automaticity, and refractory periods and, in most cardiac cells, multiple types of K+ channels that subserve these functions are expressed. Molecular cloning has revealed the presence of a large number of K+ channel pore forming (
) and accessory (ß) subunits in the heart, and considerable progress has been made recently in defining the relationships between expressed K+ channel subunits and functional cardiac K+ channels. To date, more than 20 mouse models with altered K+ channel expression/functioning have been generated using dominant-negative transgenic and targeted gene deletion approaches. In several instances, the genetic manipulation of K+ channel subunit expression has revealed the role of specific K+ channel subunit subfamilies or individual K+ channel subunit genes in the generation of myocardial K+ channels. In other cases, however, the phenotypic consequences have been unexpected. This review summarizes what has been learned from the in situ genetic manipulation of cardiac K+ channel functioning in the mouse, discusses the limitations of the models developed to date, and explores the likely directions of future research.
Key Words: Ito • IK • IK1 • mouse models • cardiac remodeling
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