Action potential variation in canine ventricle: a modeling study

An ionic model of the ventricular cell based on voltage-clamp and action potential data measured experimentally in dog heart has been developed. The model is used to test the hypothesis that spatial variation of the magnitude of I/sub to1/, I/sub Ks/, I/sub to2/, and the recovery time constant of I/sub to1/ reported in the literature can account for differences in action potential shape of epicardial (EPT), midmyocardial (M), and endocardial (ENDO) cells. The model results demonstrate that experimentally observed differences in EPI, M, and ENDO cells, that are phase 1 spike, notch, phase 3 repolarization, and rate dependence (0.5-2 Hz) of action potential duration (APD), are accounted for by the model. The simulated effects of blocking I/sub Ks/, I/sub Kr/ and I/sub to1/ also agree with experimental data in M cells. Reduction of I/sub to1/, I/sub K1/ and I/sub up/ current magnitudes and increase of I/sub NaCa/ produce prolongation of the APD in the model similar to that observed during pacing tachycardia-induced heart failure in dogs.