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See article by Taggart et al. [50] (pages 454-462) in this issue. Studies conducted over the past dozen years or so have demonstrated that ventricular myocardium is not homogeneous, as previously thought, but is comprised of at least three electrophysiologically distinct cell types: epicardial, M and endocardial cells (see [1,2] for reviews). These three cell types have also been shown to possess different pharmacologic profiles and to respond differently to a variety of pathophysiologic states [3–8].The three cells types differ principally with respect to repolarization characteristics. Ventricular epicardial and M cells display action potentials with a prominent transient outward current ( I to)-mediated phase 1, giving rise to a notched appearance of the action potential. The absence of a prominent notch in the endocardium is a consequence of a much smaller I to. Similar regional differences in I to are found in canine, feline, rabbit, rat and human ventricular myocytes (see [1] for references). Recent studies also indicate that I to and the action potential notch are much larger in right vs. left ventricular epicardial [9] and M [10] cells. The transmural gradient in the amplitude of the I to-mediated action potential notch underlies the normal J wave or J point elevation in the ECG [11] and its accentuation, particularly in the right ventricle, contributes to the development of life-threatening arrhythmias in patients with the Brugada syndrome and various forms of idiopathic ventricular fibrillation [12,13]. The presence of a prominent I to in right ventricular epicardium has also been shown to sensitize this tissue to the effects of ischemia [14]. Accentuation of the action potential notch and eventual loss of the dome in right ventricular epicardium but not endocardium has been shown to contribute to ischemia-induced ST segment elevation [12].The M cells are … *Tel.: +1-315-735-2217; fax: +1-315-735-5648 ca{at}mmrl.edu

Transmural dispersion of repolarization and the T wave