Rabbit, a relevant model for the study of cardiac β3-adrenoceptors

Abstract

The β₃-adrenoceptors (β₃-ARs) have been identified and characterized in the human heart. Specific β₃-AR stimulation, unlike β₁-AR or β₂-AR stimulation, decreases cardiac contractility, partly via the G_i–NO pathway. However, the precise role of cardiac β₃-ARs is not yet completely understood. Indeed, under normal conditions, the β₃-AR response is present only to a very low degree in rats and mice. Therefore, we evaluated whether β₃-ARs were present and functional in rabbit ventricular cardiomyocytes, and whether the rabbit could serve as a relevant model for the study of cardiac β₃-ARs. We used RT-PCR and Western blot to measure the β₃-AR transcripts and protein levels in rabbit ventricular cardiomyocytes. We also analysed the effect of β₃-AR stimulation using isoproterenol in combination with nadolol or SR 58611A on cardiomyocyte shortening, Ca²⁺ transient, L-type Ca²⁺ current (I_Ca,L), delayed rectifier potassium current (I_Ks) and action potential duration (APD). For the first time, we show that β₃-ARs are expressed in rabbit ventricular cardiomyocytes. The mRNA and protein sequences present a high homology to those of rat and human β₃-ARs. Furthermore, β₃-AR stimulation decreases cardiomyocyte shortening, Ca²⁺ transient and I_Ca,L amplitudes, via a G_i–NO pathway. Importantly, β₃-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 β₃-ARs in physiological conditions.