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Article Dans Une Revue Experimental Physiology Année : 2009

Rabbit, a relevant model for the study of cardiac beta 3-adrenoceptors

Résumé

The beta(3)-adrenoceptors (beta(3)-ARs) have been identified and characterized in the human heart. Specific beta(3)-AR stimulation, unlike beta(1)-AR or beta(2)-AR stimulation, decreases cardiac contractility, partly via the G(i)-NO pathway. However, the precise role of cardiac beta(3)-ARs is not yet completely understood. Indeed, under normal conditions, the beta(3)-AR response is present only to a very low degree in rats and mice. Therefore, we evaluated whether beta(3)-ARs were present and functional in rabbit ventricular cardiomyocytes, and whether the rabbit could serve as a relevant model for the study of cardiac beta(3)-ARs. We used RT-PCR and Western blot to measure the beta(3)-AR transcripts and protein levels in rabbit ventricular cardiomyocytes. We also analysed the effect of beta(3)-AR stimulation using isoproterenol in combination with nadolol or SR 58611A on cardiomyocyte shortening, Ca(2+) transient, L-type Ca(2+) current (I(Ca,L)), delayed rectifier potassium current (I(Ks)) and action potential duration (APD). For the first time, we show that beta(3)-ARs are expressed in rabbit ventricular cardiomyocytes. The mRNA and protein sequences present a high homology to those of rat and human beta(3)-ARs. Furthermore, beta(3)-AR stimulation decreases cardiomyocyte shortening, Ca(2+) transient and I(Ca,L) amplitudes, via a G(i)-NO pathway. Importantly, beta(3)-AR stimulation enhances I(Ks) amplitude and shortens the APD. Taken together, our results indicate that the rabbit provides a relevant model, easily used in laboratories, to study the roles of cardiac beta(3)-ARs in physiological conditions.

Dates et versions

hal-00444762 , version 1 (07-01-2010)

Identifiants

Citer

Leslie Audigane, Benoit Gilles Kerfant, Aziza El Harchi, Ilka Lorenzen-Schmidt, Gilles Toumaniantz, et al.. Rabbit, a relevant model for the study of cardiac beta 3-adrenoceptors. Experimental Physiology, 2009, 94 (4), pp.400-411. ⟨10.1113/expphysiol.2008.045179⟩. ⟨hal-00444762⟩
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