1. ¹Second Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary
2. ²Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
3. ³Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
4. ⁴Department of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary
5. ⁵Institute of Biology, University of Szeged, Szeged, Hungary
6. ⁶Department of Physiology, University of Debrecen, Debrecen, Hungary

Correspondence: Dr A Farkas, Second Department of Internal Medicine and Cardiology Centre, University of Szeged, Korányi fasor 6., Szeged H-6720, Hungary. E-mail: farkasa@in2nd.szote.u-szeged.hu

Received 18 December 2007; Accepted 12 January 2008; Published online 10 March 2008.

Abstract

Background and purpose: The Na⁺/Ca²⁺ exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na⁺ concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 M SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na⁺ concentrations in rabbit and rat hearts.

Experimental approach: The concentration-dependent effects of SEA0400 on I_Na/Ca were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.

Key results: SEA0400 inhibited I_Na/Ca with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 M SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.

Conclusions and implications: NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na⁺ concentration may play an important role in the contractility response to NCX inhibition.