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 cell s have not been separated according to their original localization. Hu man ventricular myocytes were isolated from separated subepicardial an d subendocardial tissue, and regional variations in I-to were studied. I-to was larger in subepicardial than subendocardial cells. Current d ensity 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 expla nted failing and nonfailing donor hearts were compared, I-to was not d ifferent in subepicardial cells; however, it was larger in subendocard ial cells from nonfailing hearts. The potential of half-maximal activa tion (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 w as no difference in V-0.5 between cells from failing and nonfailing he arts. I-to inactivation was similar in all cell types and independent of membrane depolarization (time constant [tau]=approximate to 60 mill iseconds 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 millis econds, n=6), exceeding control values transiently (overshoot), and sl ow at -40 mV without overshoot (tau=638+/-91 milliseconds, n=6). In su bendocardial cells, I-to recovered at -100 mV with a fast phase (tau=2 5 milliseconds) and a slow phase (tau-328 milliseconds), and recovery was not complete after 6 seconds at -100 mV. In conclusion, regional d ifferences in I-to between subepicardial and subendocardial cells may have clinical implications with respect to rhythmic disturbance during heart failure.