I-TO AND ACTION-POTENTIAL NOTCH ARE SMALLER IN LEFT VS RIGHT CANINE VENTRICULAR EPICARDIUM

Transmural heterogeneities of repolarizing currents underlie prominent differences in the electrophysiology and pharmacology of ventricular epicardial, endocardial, and M cells in a number of species. The degre e to which heterogeneities exist between the right and left ventricles is not well appreciated. The present study uses standard microelectro de and whole cell patch-clamp techniques to contrast the electrophysio logical characteristics and pharmacological responsiveness of tissues and myocytes isolated from right (RVE) and left canine ventricular epi cardium (LVE). RVE and LVE studied under nearly identical conditions d isplayed major differences in the early repolarizing phases of the act ion potential. The magnitude of phase 1 in RVE was nearly threefold th at in LVE: 28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV (basic cycle length = 2,00 0 ms). Phase 1 in RVE was also more sensitive to alterations of the st imulation rate and to 4-aminopyridine (4-AP), suggesting a much greate r contribution of the transient outward current (I-to 1) in RVE than i n LVE. The combination of 4-AP plus ryanodine, low chloride, or 4,4'-d iisothiocyanostilbene-2,2'-disulfonic acid (chloride channel blocker) completely eliminated the notch and all rate dependence of the early p hases of the action potential, making RVE and LVE indistinguishable. A t +70 mV, RVE myocytes displayed peak I-to 1 densities between 28 and 37 pA/pF. LVE myocytes included cells with similar 1,1 densities (thou ght to represent subsurface cells) but also cells with much smaller cu rrent levels (thought to represent surface cells). Average peak I-to 1 density was significantly smaller in LVE than in RVE at voltages more than or equal to +10 mV. Our data point to prominent differences in t he magnitude of the I-to 1-mediated action potential notch in cells at the surface of RVE compared with the LVE and suggest that important d istinctions may exist in the response of these two tissues to pharmaco logical agents and pathophysiological states, as previously demonstrat ed for epicardium and endocardium. Our findings also suggest that a ca lcium-activated outward current contributes to the early repolarizatio n phase in RVE and LVE and that the influence of this current, althoug h small, is more important in the left ventricle.