1. ¹Department of Pharmacology & Pharmacotherapy, Albert Szent-Györgyi Medical Center, Faculty of Medicine, University of Szeged, Dóm tér 12, PO Box 427, Szeged, Hungary
2. ²Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
3. ³Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

Correspondence: Andras Varro, Department of Pharmacology & Pharmacotherapy, Albert Szent-Györgyi Medical Center, Faculty of Medicine, University of Szeged, Dóm tér 12, PO Box 427, Szeged, Hungary. E-mail: varro@phcol.szote.u-szeged.hu

Received 2 June 2004; Revised 27 July 2004; Accepted 22 September 2004; Published online 25 October 2004.

Abstract

The sodium–calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37°C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 M SEA-0400 from 26.62.5 to 14.81.8 mV (n=9, P<0.05) and from 12.51.7 to 5.91.4 mV (n=3, P<0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.