title: Activation of β(3)-adrenoceptor promotes rapid pacing-induced atrial electrical remodeling in rabbits.
abstract: Cardiac electrophysiological function is under the regulatory control of the sympathetic nervous system. In addition to classical β-adrenoceptors (β-AR, including β(1)- and β(2)- subtypes), β(3)-AR is also expressed in human heart and shows its distinctive functions. This study is aimed to elucidate the role of β(3)-AR in the regulation of atrial fibrillation (AF), especially its role in rapid pacing-induced atrial electrical remodeling in rabbits. The rapid atrial pacing model was established by embedding electrodes in the right atrium pacing at a speed of 600 beats per minute. The protein level of β(3)-AR in the atria was found significantly upregulated by western blot. The atrial effective refractory period (AERP) and its rate adaptation were decreased after pacing which were further shortened by BRL37344, a selective β(3)-AR agonist, leading to the increase of AF inducibility and duration. Similarly, β(3)-AR activation induced time-dependent shortening of action potential duration (APD), together with decrease of L-type calcium current (I(Ca,L)) and increase of inward rectifier potassium current (I(K1)) and transient outward potassium current (I(to)) in rapid pacing atrial myocytes. Meanwhile, all the effects were abolished by specific β(3)-AR antagonist, SR59230A. In summary, our study represents that activation of β(3)-AR promotes the atrial electrical remodeling process by altering the balance of ion channels in atrial myocytes, which provides new insights into the pharmacological role of β(3)-AR in heart diseases.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, RP China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Yu
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Lanfeng
authors.initials: L
authors.lastname: Wang
authors.forename: Deli
authors.initials: D
authors.lastname: Dong
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D004566:Electrodes; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism / Q000502:physiology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology
chemical_list: C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D020746:Calcium Channels, L-Type; D024661:Potassium Channels, Inwardly Rectifying; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3