Transient outward current in human and rat ventricular myocytes

Objective: The aim was to investigate transient outward currents (Ito) 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. Methods: Using the whole cell patch clamp technique, depolarisation dependent Ito was investigated in these myocytes, and its electrophysiological characteristics compared to Ito of rat myocytes. Results: Ito was observed in ventricular myocytes isolated from failing and non-failing human hearts. The current density of Ito 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 Ito in human (n=17) and 39(5)% in rat cells (n=12). The potential of half maximum steady state inactivation of rapidly inactivating Ito 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 Ito 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. Conclusions: In a limited number of cells, Ito in human ventricular myocytes shows no dramatic differences between cells derived from failing and non-failing hearts. The characteristics of Ito in human cells were similar though not identical to Ito in rat heart cells. This current may be a potential target for antiarrhythmic drug action. Cardiovascular Research 1993;27:1662-1669