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Tuning repolarization in the heart: a multitude of potassium channels and regulatory pathways.

A pproximately one decade after the cloning of the first potassium channel, potassium channel genes of amazing diversity have emerged, many of them expressed in the heart. A magnitude of a subunits forming homotetramers or heterotetramers, multiple regulatory subunits, and alternative splicing of genes adds up to a seemingly endless diversity of potassium channels. Considering the relative uniformity of the major cardiac inward currents, most of the heterogeneity in action potential waveforms among different species and anatomical regions seems to be related to differences in potassium channel expression. Recent attention has focused on electrical heterogeneity within atrial and ventricular myocardium, which also seems predominantly to reflect differences in potassium channel expression. Most of these studies have been done on a functional level; now information about molecular substrates of regional electrical heterogeneity is emerging. Because of the essential importance for identification of potential targets for therapeutic interventions, much attention has recently focused on 2 aspects: elucidation of the molecular identity of cardiac potassium channels and their correlation to currents, including regional heterogeneity, and identification of regulatory pathways relevant to ion channel expression under normal and pathological conditions.