TRANSIENT OUTWARD CURRENT IN HUMAN VENTRICULAR MYOCYTES OF SUBEPICARDIAL AND SUBENDOCARDIAL ORIGIN

In various mammalian species, shapes of action potentials vary within the cardiac wall because of differences in transient outward current (I-to). A prominent I-to exists in human ventricular myocytes, but cells have not been separated according to their original localization. Human ventricular myocytes were isolated from separated subepicardial and subendocardial tissue, and regional variations in I-to were studied. I-to was larger in subepicardial than subendocardial cells. Current density at +60 mV was 7.9+/-0.7 pA/pF (n=28) in subepicardial cells and 2.3+/-0.3 pA/pF (n=16) in subendocardial cells. When cells from explanted failing and nonfailing donor hearts were compared, I-to was not different in subepicardial cells; however, it was larger in subendocardial cells from nonfailing hearts. The potential of half-maximal activation (V-0.5) was more positive in subendocardial cells (+25.6 +/- 3.5 mV, n=15) than in subepicardial cells (+9.2 +/- 1.8 mV, n=28). There was no difference in V-0.5 between cells from failing and nonfailing hearts. I-to inactivation was similar in all cell types and independent of membrane depolarization (time constant [tau]=approximate to 60 milliseconds at 22 degrees C). The potential of half-maximal steady-state inactivation was similar in all cell types. Recovery from inactivation of I-to was fast in subepicardial cells at -100 mV (tau=24+/-4 milliseconds, n=6), exceeding control values transiently (overshoot), and slow at -40 mV without overshoot (tau=638+/-91 milliseconds, n=6). In subendocardial cells, I-to recovered at -100 mV with a fast phase (tau=25 milliseconds) and a slow phase (tau-328 milliseconds), and recovery was not complete after 6 seconds at -100 mV. In conclusion, regional differences in I-to between subepicardial and subendocardial cells may have clinical implications with respect to rhythmic disturbance during heart failure.