BASIC CARDIAC ELECTROPHYSIOLOGY - CELLULAR AND MOLECULAR MECHANISMS OF DEPOLARIZATION AND REPOLARIZATION

The properties of cardiac impulse propagation are governed largely by the interplay of cellular depolarization, repolarization, cellular excitability, and myocardial tissue anisotropy. During the last decade, the introduction of the patch-clamp technique, which allows recording of ionic current flow through a single ion channel, provided insight into the mechanism of depolarization and repolarization in various cardiac cell types. The culmination of work in the field of molecular biology led to the cloning and functional expression of ion channel proteins. It is now possible to introduce systematic changes in ion channel protein structure to study the structure-function relationship and antiarrhythmic drug-binding sites on the ion channel. Such specific alterations in ion channel protein structure may help in the design of drugs with specific binding properties to suit a given clinical goal (arrhythmia management or suppression or both). However, it must be remembered that the phenomenon of arrhythmia suppression must ultimately be studied at the tissue (multicellular) level, because tissue models are the only practical means to evaluate and appreciate the interaction of depolarization and repolarization in impulse propagation. Hopefully, during the next decade, information coming from the two different approaches (molecular versus tissue) can be integrated to provide insight to various mechanisms of arrhythmia suppression or arrhythmia aggravation (proarrythmia) or both.