β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current

Autor: Zablockaite D, Gendviliene, Bogdelis A, Jonas Jurevičius, Vytenis Arvydas Skeberdis, Rimantas Treinys, Regina Macianskiene, Rodolphe Fischmeister
Přispěvatelé: Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2008
Předmět:
Zdroj: Journal of Clinical Investigation
Journal of Clinical Investigation, American Society for Clinical Investigation, 2008, ⟨10.1172/JCI32519⟩
ISSN: 0021-9738
DOI: 10.1172/jci32519
Popis: International audience; There has been a large body of evidence indicating that β3-adrenergic receptor (β3-AR) activation produces a negative inotropic effect in human ventricle. Here, we explored the role of this receptor in human atrium. Unexpectedly, we found that β3-AR activation increases contractility in human atrial tissue and stimulates the L-type Ca 2+ channel current (ICa,L) in isolated human atrial myocytes (HAMs). Specimens of right atrial tissues were obtained from 57 patients undergoing heart surgery for congenital defects, coronary artery diseases, valve replacement or heart transplantation. ICa,L was recorded using the whole-cell patch-clamp technique and isometric contraction was recorded using a mechanoelectrical force transducer. Two selective β3-AR agonists, SR58611 and BRL37344, and a β3-AR partial agonist, CGP12177 stimulated ICa,L in HAMs with nanomolar potency and 60 to 90% efficacy as compared to isoprenaline. They also increased contractility but with a much lower efficacy (~10%) than isoprenaline. The β3-AR antagonist L-748,337, the β1-/β2-AR antagonist nadolol, and the β1-/β2-/β3-AR antagonist bupranolol were used to confirm the involvement of β3-ARs (and not β1-/β2-ARs) in these effects. β3-AR effects involved the cAMP/PKA pathway because the stimulation of ICa,L was blocked by the PKA inhibitor H89, and the positive inotropic effect was strongly increased by the phosphodiesterase inhibitor, IBMX. These results indicate that, unlike in ventricular tissue, β3-ARs are positively coupled to L-type Ca 2+ channels and contractility in human atrial tissue through cAMP-dependent pathway.
Databáze: OpenAIRE