Differences in transient outward currents of feline endocardial and epicardial myocytes

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 (I(to)) 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 I(to), whereas in endocardial cells the notch in action potentials and I(to) were small. External application of 4-aminopyridine (2 mM) reduced the amplitudes of notch and I(to) in epicardial cells but not in endocardial cells. After application of 4-aminopyridine (2 mM) and caffeine (5 mM), the notch and I(to) were abolished completely in both endocardial and epicardial cells. The first component of I(to) (I(to1)) was present in all epicardial cells studied (n = 20); it was absent in 12 of the 20 endocardial cells, and a small I(to1) was present in the remaining eight endocardial cells. The mean amplitude of I(to1) was significantly greater in epicardial than in endocardial cells. At a test voltage of +80 mV, the amplitude of I(to1) 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 I(to) (I(to2)) was present in all endocardial (n = 30) and epicardial (n = 30) cells studied. The amplitude of I(to2) was significantly greater in epicardial than in endocardial cells. At a test voltage of +60 mV, the amplitude of I(to2) 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 I(to) in endocardial and epicardial myocytes may relate to regional heterogeneity of electrical properties of the heart.