14th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 2000

Jan. 29 - Feb. 5, 2000
Marilleva, Trento, Italy

RT-32

Pacemaker current in human ventricular myocytes: modulation and role in arrhythmogenesis

Laura Sartiani, Elisabetta Cerbai, Petra DePaoli, Alessandro Mugelli.
Department of Preclinical and Clinical Pharmacology, University of Firenze, Italy

Abstract

BACKGROUND. Electrophysiological alterations (e.g. prolongation of the action potential duration and occurrence of the pacemaker current I_f) are typically present in ventricular myocytes from the failing human heart and are likely to play an arrhythmogenic role. Several studies in animal models of cardiac hypertrophy and failure have documented that a- and b-adrenergic receptors are able to affect the action potential duration, the steepness of diastolic depolarization and the amplitude of I_f current.

METHODS. Left ventricular myocytes were prepared using enzymatic procedures from hearts explanted for terminal heart failure. Action potentials and ionic currents were recorded using the patch-clamp technique.

RESULTS. The action potential recorded from human ventricular myocytes was prolonged by both a- and b-adrenoceptor stimulation. b-Adrenoceptor stimulation also increased the steepness of diastolic depolarization and the amplitude of the pacemaker current I_f, by shifting its activation curve toward less negative values. A₁-Purinergic stimulation reversed these effects. a-Adrenoceptor stimulation did not affect the steepness of diastolic depolarization and the amplitude and activation curve of I_f.

CONCLUSIONS. Our results demonstrate that a- and b-adrenoceptor stimulation by catecholamines modulates the extent of the alterations occurring in the human failing myocardium, thus likely amplifying their arrhythmogenic role.

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