Computed action potentials, using the Luo-Rudy simulation (94) modified to include a transient outward current. This simulation incorporates physiologically realistic numerical models of individual ion currents and other electrogenic events (e.g., exchangers) and thereby allows in silico prediction of the effects of lesions in individual components on the whole physiologic system. A and B each show (from top to bottom) epicardial action potential, I_Kr and I_Ks during the epicardial action potential, midmyocardial action potential, I_Kr and I_Ks during the midmyocardial action potential, and an ECG signal computed from a 1-dimensional fiber consisting of endocardial, midmyocardial, and epicardial cells connected through resistive gap junctions (95). (A) Control. The numbered phases of the action potential are shown on the epicardial signal. Note the increase in I_Kr at the beginning of phase 3; as discussed in the text, this serves to enhance repolarization. The dotted lines indicate the ends of repolarization in the epicardial and midmyocardial cells and correspond roughly to the peak and end of the T wave, respectively. (B) 75% I_Kr blockade. Note that action potentials at both sites are prolonged, and the difference between them is exaggerated. The T wave abnormality in the computed ECG also reflects formation of EADs in endocardial cells (not shown).