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Cardiovascular Research 1995 30(3):440-448; doi:10.1016/S0008-6363(95)00073-9
© 1995 by European Society of Cardiology
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Copyright © 1995, European Society of Cardiology

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

Daniel Potreau*, Jean Pierre Gomez and Nassim Fares

Laboratory of General Physiology, URA CNRS 1869, University of Poitiers, 40 Au du Recteur Pineau, F-86022 Poitiers Cédex, France

* Corresponding author. Tel. (+33) 49453955; Fax (+33) 49454014.

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.

KEYWORDS Hypertrophy; Voltage clamp; Potassium channel, transient outward; Ferret, ventricular myocytes


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