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

In the mammalian heart, Ca 2+ -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.