Genetic manipulation of cardiac K(+) channel function in mice: what have we learned, and where do we go from here?

Circ Res. 2001 Nov 23;89(11):944-56. doi: 10.1161/hh2301.100349.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Action Potentials
  • Animals
  • Delayed Rectifier Potassium Channels
  • Disease Models, Animal*
  • Electric Conductivity
  • Forecasting
  • Heart / physiology*
  • Heart Diseases / etiology
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Potassium Channels / genetics*
  • Potassium Channels / physiology*
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / physiology
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / physiology


  • Delayed Rectifier Potassium Channels
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Potassium Channels, Voltage-Gated