OUP user menu

Transient outward current in human and rat ventricular myocytes

Erich Wettwer , Gregory Amos , Jennifer Gath , Hans-Reinhard Zerkowski , Jürgen-Christoph Reidemeister , Ursula Ravens
DOI: http://dx.doi.org/10.1093/cvr/27.9.1662 1662-1669 First published online: 1 September 1993

Abstract

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

Key terms
  • human ventricular cardiac myocytes
  • membrane currents
  • transient outward current (Ito)

    Sign in

    ESC members Follow the 'ESC Member and Congress Delegate Sign In' link below for free online access if your subscription to this journal is via the European Society of Cardiology, either as a member or an ESC Congress delegate. Discover if you are an ESC member here.

    Otherwise, if your subscription is via OUP, enter your OUP username and password, or select an alternative sign in option below.

    Log in through your institution