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 (alpha) and accessory (beta) 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.
- 11717150
- action
- animal,
- animals,
- channels,
- conductivity,
- disease
- diseases,
- electric
- forecasting,
- gov't,
- heart
- heart,
- humans,
- inwardly
- knockout,
- mice,
- models,
- non-u.s.
- p.h.s.,
- potassium
- potentials,
- rectifying,
- research
- support,
- transgenic,
- u.s.
- voltage-gated,
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