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

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

RT-33

Arrhythmogenic mechanisms of norepinephrine in depolarized single ventricular myocytes

Yejia Song, Mario Vassalle.
Department of Physiology and Pharmacology, State University of New York, Health Science Center, New York, USA

Introduction

Electrical depolarization may induce diastolic depolarization (DD) in myocardial tissues, both in multicellular preparations¹ and in single myocytes². Since norepinephrine steepens diastolic depolarization of pacemaker tissues, the question arises whether norepinephrine should increase the slope of diastolic depolarization and cause spontaneous discharge also in depolarized myocytes. The clinical relevance of this question resides in the fact that, in certain conditions (e.g. ischemia), there may be at the same time depolarization of myocardial cells and an increased release of catecholamines.

Alternative possibilities should also be considered, since norepinephrine increases the slow inward current I_Ca. In turn, the consequent increase in intracellular calcium would facilitate the appearance of oscillatory potentials (V_os or afterdepolarization; see Yang and Vassalle³). Depolarization also facilitates the appearance of oscillatory potentials⁴ and of the underlying oscillatory current (I_os) in Purkinje fibers⁵ as well as in single myocytes². The combination of increased I_Ca and of depolarization might then induce V_os of sufficient magnitude to initiate spontaneous activity. Our aims were to determine whether NE facilitate spontaneous discharge in depolarized myocytes and to study the underlying mechanism. Membrane potentials and currents were recorded in guinea pig single myocytes, which were electrically depolarized in the absence and presence of NE to clarify the mechanism by which NE may modify DD and cause spontaneous activity.