Repolarizing K + Currents in Nonfailing Human Hearts

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Abstract
Background Studies of cardiac K + channels from animal models have documented tissue-dependent and species-dependent diversity in the types and properties of K + channels responsible for the repolarization of cardiac action potentials. Recent reports of human ventricular K + currents emphasized differences in transient outward K + current (I to1 ) recorded from left ventricular (LV) subendocardial and subepicardial myocytes. These myocytes are usually isolated only from the LV free wall. The surface of the interventricular septum is continuous with the endocardium of both ventricular chambers. However, the septum contracts in unison with the left ventricle and therefore might have electric properties consonant with this function. In this study, we compare the characteristics of human cardiac K + currents (I to1 and inward rectifier K + current [I K1 ]) of myocytes isolated from either the LV subepicardium or subendocardium of the right ventricular (RV) septum. Methods and Results Subendocardial tissues were obtained during routine biopsies of the right interventricular septum of seven heart transplant recipients. Subepicardial tissues were obtained from five patients with normal LV function during open heart surgery. I K1 amplitude was the same in myocytes isolated from both regions. Delayed rectifier K + currents were small or absent in these cells. I to1 was only slightly larger in LV subepicardial versus RV septal subendocardial myocytes. For example, at +60 mV, I to1 was 7.2±0.4 pA/pF (n=33) in subepicardial cells compared with 6.0±0.5 pA/pF (n=36) in subendocardial cells. All characteristics of I to1 examined, including the voltage dependence of activation and inactivation, rate of inactivation, and percent decline of peak current during repetitive pulsing, were similar in myocytes isolated from both regions. These findings are in contrast to previous studies that demonstrated that I to1 of subendocardial myocytes isolated from the LV free wall of human hearts was smaller and that recovery from inactivation of this current was much slower compared with that observed in subepicardial myocytes. Conclusions We conclude that the major repolarizing K + currents in normal human ventricular myocytes are I K1 and I to1 and that the properties of I to1 of subendocardial cells isolated from the right interventricular septum are more similar to subepicardial cells than to subendocardial cells of the LV free wall. The similar electric properties shared by myocytes from these two regions may be functionally important inasmuch as the right side of the interventricular septum functions as an extension of the subepicardium of the left ventricle during the contractile cycle.