REPOLARIZING K- SIMILARITIES BETWEEN RIGHT SEPTAL SUBENDOCARDIAL AND LEFT SUBEPICARDIAL VENTRICULAR MYOCYTES( CURRENTS IN NONFAILING HUMAN HEARTS )

Background Studies of cardiac K+ channels from animal models have docu mented tissue-dependent and species-dependent diversity in the types a nd properties of K+ channels responsible for the repolarization of car diac action potentials. Recent reports of human ventricular K+ current s emphasized differences in transient outward K+ current (I-to1) recor ded from left Ventricular (LV) subendocardial and subepicardial myocyt es. These myocytes are usually isolated only from the LV free wall. Th e surface of the interventricular septum is continuous with the endoca rdium of both ventricular chambers. However, the septum contracts in u nison with the left ventricle and therefore might have electric proper ties consonant with this function. In this study, we compare the chara cteristics 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 R esults Subendocardial tissues were obtained during routine biopsies of the right interventricular septum of seven heart transplant recipient s. 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 wer e 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 com pared with 6.0+/-0.5 pA/pF (n=36) in subendocardial cells. All charact eristics of I-to1 examined, including the voltage dependence of activa tion and inactivation, rate of inactivation, and percent decline of pe ak current during repetitive pulsing, were similar in myocytes isolate d from both regions. These findings are in contrast to previous studie s that demonstrated that I-to1 of subendocardial myocytes isolated fro m the LV free wall of human hearts was smaller and that recovery from inactivation of this current was much slower compared with that observ ed in subepicardial myocytes. Conclusions We Conclude that the major r epolarizing K+ currents in normal human ventricular myocytes are I-K1 and I-to1 and that the properties of I-to1 of subendocardial cells iso lated from the right interventricular septum are more similar to subep icardial cells than to subendocardial cells of the LV free wall. The s imilar electric properties shared by myocytes from these two regions m ay be functionally important inasmuch as the right side of the interve ntricular septum functions as an extension of the subepicardium of the left ventricle during the contractile cycle.