Rabbit, a relevant model for the study of cardiac beta 3-adrenoceptors.
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.
Audigane
Leslie
L
INSERM, UMR 915, l'institut du thorax, Nantes, F-44035 France.
Kerfant
Benoît-Gilles
BG
El Harchi
Aziza
A
Lorenzen-Schmidt
Ilka
I
Toumaniantz
Gilles
G
Cantereau
Anne
A
Potreau
Daniel
D
Charpentier
Flavien
F
Noireaud
Jacques
J
Gauthier
Chantal
C
D000200:Action Potentials; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009248:Nadolol / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes; D009569:Nitric Oxide; D009248:Nadolol; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007545:Isoproterenol; C076252:amibegron