Molecular basis of functional voltage‐gated K+ channel diversity in the mammalian myocardium

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Abstract
In the mammalian heart, Ca2+‐independent, depolarization‐activated potassium (K+) currents contribute importantly to shaping the waveforms of action potentials, and several distinct types of voltage‐gated K+ currents that subserve this role have been characterized. In most cardiac cells, transient outward currents, Ito,f and/or Ito,s, and several components of delayed reactivation, including IKr, IKs, IKur and IK,slow, are expressed. Nevertheless, there are species, as well as cell‐type and regional, differences in the expression patterns of these currents, and these differences are manifested as variations in action potential waveforms. A large number of voltage‐gated K+ channel pore‐forming (α) and accessory (β, minK, MiRP) subunits have been cloned from or shown to be expressed in heart, and a variety of experimental approaches are being exploited in vitro and in vivo to define the relationship(s) between these subunits and functional voltage‐gated cardiac K+ channels. Considerable progress has been made in defining these relationships recently, and it is now clear that distinct molecular entities underlie the various electrophysiologically distinct repolarizing K+ currents (i.e. Ito,f, Ito,s, IKr, IKs, IKur, IK,slow, etc.) in myocyardial cells.