Genetic Manipulation of Cardiac K+ Channel Function in Mice: What Have We Learned, and Where Do We Go From Here?

JM Nerbonne, CG Nichols, TL Schwarz… - Circulation …, 2001 - Am Heart Assoc
JM Nerbonne, CG Nichols, TL Schwarz, D Escande
Circulation research, 2001Am Heart Assoc
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 (α) and accessory (β)
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 …
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 (α) and accessory (β) 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.
Am Heart Assoc