TY - JOUR
T1 - Genetic manipulation of cardiac K+ channel function in mice
T2 - What have we learned, and where do we go from here?
AU - Nerbonne, Jeanne M.
AU - Nichols, Colin G.
AU - Schwarz, Thomas L.
AU - Escande, Denis
PY - 2001/11/23
Y1 - 2001/11/23
N2 - 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.
AB - 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.
KW - Cardiac remodeling
KW - I
KW - I
KW - I
KW - Mouse models
UR - http://www.scopus.com/inward/record.url?scp=0035940747&partnerID=8YFLogxK
U2 - 10.1161/hh2301.100349
DO - 10.1161/hh2301.100349
M3 - Review article
C2 - 11717150
AN - SCOPUS:0035940747
SN - 0009-7330
VL - 89
SP - 944
EP - 956
JO - Circulation research
JF - Circulation research
IS - 11
ER -