Abstract
Whole-cell voltage-clamp experiments were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to test the hypothesis that the differences in the amplitude of transient outward current (Ito) contribute to the difference in action potential configuration between endocardial and epicardial myocytes. In the control state, action potentials recorded from epicardial cells demonstrated a prominent notch between phases 1 and 2, and membrane current recordings displayed a prominent Ito, whereas in endocardial cells the notch in action potentials and Ito were small. External application of 4-aminopyridine (2 mM) reduced the amplitudes of notch and Ito in epicardial cells but not in endocardial cells. After application of 4-aminopyridine (2 mM) and caffeine (5 mM), the notch and Ito were abolished completely in both endocardial and epicardial cells. The first component of Ito (Ito1) was present in all epicardial cells studied (n=20); it was absent in 12 of the 20 endocardial cells, and a small 1to1 was present in the remaining eight endocardial cells. The mean amplitude of Ito1 was significantly greater in epicardial than in endocardial cells. At a test voltage of +80 mV, the amplitude of Ito1 was 102.0±47.7 pA/pF in epicardial cells and 3.3±3.3 pA/pF in endocardial cells (p<0.01). The second component of Ito (Ito2) was present in all endocardial (n=30) and epicardial (n=30) cells studied. The amplitude of Ito2 was significantly greater in epicardial than in endocardial cells. At a test voltage of +60 mV, the amplitude of Ito2 was 10.8±4.1 pA/pF in epicardial cells and 8.1±4.9 pA/pF in endocardial cells (p<0.05). The differential distribution of Ito in endocardial and epicardial myocytes may relate to regional heterogeneity of electrical properties of the heart.
