Transient outward current in human and rat ventricular myocytes.

Abstract

The aim was to investigate transient outward currents (I(to)) in single myocytes isolated from human heart muscle specimens which were obtained either from patients in terminal heart failure receiving a transplant or from multiorgan donors whose hearts were not suitable for transplantation. Using the whole cell patch clamp technique, depolarisation dependent I(to) was investigated in these myocytes, and its electrophysiological characteristics compared to I(to) of rat myocytes. I(to) was observed in ventricular myocytes isolated from failing and non-failing human hearts. The current density of I(to) was similar in cells from failing and non-failing hearts [at +60 mV: 7.9(SEM 1.0) pA.pF-1, n = 9, and 8.7(1.2) pA.pF-1, n = 8, respectively], but smaller in human than in normal rat myocytes, ie, 8.2(0.7) pA.pF-1 (n = 17) v 19.9(2.8) pA.pF-1 (n = 12, six hearts), respectively. Half maximum activation was found at more positive potentials in human than in rat cells, at +21.2(2.0) v +6.4(1.3) mV. In human myocytes, the fraction of non-inactivating outward current at the end of 300 ms long clamp steps was smaller than in rat cells, ie, 22(5%) of peak I(to) in human (n = 17) and 39(5%) in rat cells (n = 12). The potential of half maximum steady state inactivation of rapidly inactivating I(to) in the presence of 0.1 mM Cd2+ was -21.4(0.7) mV in human (n = 15, five hearts), and -35.3(1.0) mV in rat cells (n = 12, six hearts). The late component of outward current showed no potential dependent inactivation in human cells, but underwent steady state inactivation at all potentials positive to -100 mV in rat myocytes. At -100 mV, recovery of I(to) from inactivation took place with a similar time constant, ie, 18(2) ms (n = 7), 24(2) ms (n = 6), and 25(2) ms (n = 4) in cells from three failing and two non-failing human hearts, and from two normal rat hearts, respectively. In a limited number of cells, I(to) in human ventricular myocytes shows no dramatic differences between cells derived from failing and non-failing hearts. The characteristics of I(to) in human cells were similar though not identical to I(to) in rat heart cells. This current may be a potential target for antiarrhythmic drug action.