CHARACTERISTICS OF THE DELAYED RECTIFIER CURRENT (I-KR AND I-KS) IN CANINE VENTRICULAR EPICARDIAL, MIDMYOCARDIAL, AND ENDOCARDIAL MYOCYTES - A WEAKER I-KS CONTRIBUTES TO THE LONGER ACTION-POTENTIAL OF THE M-CELL

Recent studies have described regional differences in the electrophysi ology and pharmacology of ventricular myocardium in canine, feline, ra t, guinea pig, and human hearts. In this study, we use standard microe lectrode and whole-cell patch-clamp techniques to examine the characte ristics of the action potential and the delayed rectifier K+ current ( I-K) in epicardial, M region (deep subepicardial to midmyocardial), an d endocardial cells isolated from the canine left ventricle. Cells fro m the M. region displayed much longer action potential durations (APDs ) at slow rates. At a basic cycle length of 4 s, APD measured at 90% r epolarization was 358+/-16 (mean+/-SEM), 262+/-12, and 287+/-11 ms in cells from the M region, epicardium, and endocardium, respectively. St eady state APD-rate relations were steeper in cells from the M region. In complete Tyrode's solution, I-K was smaller in myocytes from the M region when compared with those isolated from the epicardium or endoc ardium. Further characterization of I-K was conducted in a Na+-, K+-, and Ca2+-free bath solution to isolate the slowly activating component of the delayed rectifier (I-Ks) from the rapidly activating component (I-Kr). I-Ks was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to -20 mV, I-Ks tail curren t density was 1.99+/-0.30 pA/pF (mean+/-SEM) in epicar dial cells, 1.8 3+/-0.18 pA/pF in endocardial cells, and 0.92+/-0.14 pA/pF in M cells. Voltage dependence and time course of activation and deactivation of I-Ks were similar in the three cell types. The relative contribution o f I-Kr and I-Ks among the three cell types was examined by using 6 mmo l/L [K+](o) Tyrode's solution with and without E-4031, a highly select ive blocker of I-Kr. An E-4031-sensitive current was observed in the p resence but not in the absence of extracellular K+. This rapidly activ ating component showed characteristics similar to those of I-Kr as des cribed in rabbit and cat ventricular cells. Deactivation of I-Kr was s ignificantly slower than that of I-Ks. I-Kr (E-4031-sensitive componen t) tail current density was similar in the three cell types, whereas I -Ks (E-4031-insensitive component) tail current density was significan tly smaller in the M cells. Our results suggest that the distinctive p hase-3 repolarization features of M cells are due in part to a lesser contribution of I-Ks and that this distinction may also explain why M cells are the main targets for agents that prolong APD in ventricular myocardium. These findings may advance our understanding of the ionic basis for the electrocardiographic T wave, U wave, and long QT interva ls as well as our understanding of factors contributing to the develop ment of cardiac arrhythmias.