K+ channels and control of ventricular repolarization in the heart.

K+ channels form a large family, in which voltage-operated and ligand-operated channels can be distinguished. Under physiological conditions, four K+ currents contribute to the repolarization process and their role is discussed: i) the transient outward current (ito) is responsible for the rapid initial repolarization process from the crest of the action potential to the plateau level; ii) the delayed K+ current (iK) is involved in the overall repolarization process during the plateau; iii) the inward rectifier (iK1) is responsible for the final rapid repolarization and the maintenance of the resting potential; iv) a ligand-operated channel activated by acetylcholine and adenosine participates in the repolarization process and the maintenance of the resting potential in nodal, atrial and Purkinje cells. In the context of antiarrhythmic interventions, block of outward K+ current and prolongation of refractoriness is currently considered as an alternative to block of the Na+ current and reduction of conduction velocity. Although some of these drugs show use-dependent block, the frequency-dependent changes in current and action potential duration are not ideal.