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 |
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Přispěvatelé: | Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM) |
Rok vydání: | 2008 |
Předmět: |
Adult
Male Inotrope medicine.medical_specialty Patch-Clamp Techniques IBMX Calcium Channels L-Type Adrenergic beta-3 Receptor Agonists 030204 cardiovascular system & hematology Biology Nitric Oxide Models Biological Contractility 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Nadolol Internal medicine Isoprenaline medicine Humans Heart Atria Phosphodiesterase inhibitor Aged 030304 developmental biology Aged 80 and over Muscle Cells 0303 health sciences Dose-Response Relationship Drug Antagonist General Medicine Middle Aged 3. Good health Endocrinology chemistry Receptors Adrenergic beta-3 Bupranolol Female Research Article medicine.drug |
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 |
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