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Type of publication: research article
Type of publication (PDB): Straipsnis Clarivate Analytics Web of Science / Article in Clarivate Analytics Web of Science (S1)
Field of Science: Biofizika / Biophysics (N011)
Author(s): Skeberdis, Vytenis Arvydas;Gendvilienė, Vida;Zablockaitė, Danguolė;Treinys, Rimantas;Mačianskienė, Regina;Bogdelis, Andrius;Jurevičius, Jonas;Fischmeister, Rodolphe
Title: β3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current
Is part of: Journal of clinical investigation. Ann Arbor : American Society for Clinical Investigation, Vol. 118, no. 9 (2008)
Extent: p. 3219–3227
Date: 2008
Note: CA WOS antraštė: beta(3)-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current
Keywords: Receptors;Adrenergic;Beta-3;Calcium channels;L-Type;Myocardial contraction;Heart atria
Abstract: β3-adrenergic receptor (β3-AR) activation produces a negative inotropic effect in human ventricles. Here we explored the role of β3-AR in the human atrium. Unexpectedly, β3-AR activation increased human atrial tissue contractility and stimulated the L-type Ca2+ channel current (ICa,L) in isolated human atrial myocytes (HAMs). Right atrial tissue specimens were obtained from 57 patients undergoing heart surgery for congenital defects, coronary artery diseases, valve replacement, or heart transplantation. The ICa,L and isometric contraction were recorded using a whole-cell patch-clamp technique and 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 a 60%–90% efficacy compared with isoprenaline. The β3-AR agonists also increased contractility but with a much lower efficacy (~10%) than isoprenaline. The β3-AR antagonist L-748,337, β1-/β2-AR antagonist nadolol, and β1-/β2-/β3-AR antagonist bupranolol were used to confirm the involvement of β3-ARs (and not β1-/β2-ARs) in these effects. The β3-AR effects involved the cAMP/PKA pathway, since the PKA inhibitor H89 blocked ICa,L stimulation and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) strongly increased the positive inotropic effect. Therefore, unlike in ventricular tissue, β3-ARs are positively coupled to L-type Ca2+ channels and contractility in human atrial tissues through a cAMP-dependent pathway
Affiliation(s): Kauno medicinos universiteto Kardiologijos institutas
Appears in Collections:Universiteto mokslo publikacijos / University Research Publications

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