Depressed transient outward current in single hypertrophied cardiomyocytes isolated from the right ventricle of ferret heart

Abstract

Objective: The aim of this study was to investigate transient outward potassium current (Ito) changes as a basis for the prolongation of the action potential associated with cardiac hypertrophy.

Methods: Right ventricular hypertrophy was induced by chronic pulmonary artery constriction in adult male ferrets. After 4-6 weeks, hearts were excised and single myocytes were isolated from the right ventricles of banded and sham-operated (control) animals by enzymatic dissociation. Ito was recorded by means of the whole cell patch clamp technique.

Results: Heart weight:body weight ratio and cell membrane capacitance, as indications of hypertrophy, were increased by 17% (P < 0.05) and 32% (P < 0.01) respectively in the banded group. Analysis of Ito showed that in hypertrophied myocytes compared to normal controls: (1) the density of current was significantly reduced; (2) both the time to peak and the time constant of inactivation were increased; (3) the voltage-dependent steady-state availability was not changed, with similar potentials for half activation (30.4 +/- 6.8 mV in control and 33.9 +/- 8.5 mV in hypertrophied cells) and half inactivation (-12.3 +/- 3.3 mV in control and -11.4 +/- 2.7 mV in hypertrophied cells); (4) the time constant for recovery from inactivation was significantly increased regardless of the holding potentials (-50 mV, -70 mV or -90 mV).

Conclusions: Alterations of the transient outward potassium current with respect to its density, kinetics and recovery from inactivation can explain the prolongation of the action potential in myocytes isolated from pressure-overload hypertrophied heart and may thus be an important step in such cardiac adaptation.