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

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, I(to,f) and/or I(to,s), and several components of delayed reactivation, including I(Kr), I(Ks), I(Kur) and I(K,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. I(to,f), I(to,s), I(Kr), I(Ks), I(Kur), I(K,slow), etc.) in myocyardial cells.