Activation of β3-Adrenoceptor Promotes Rapid Pacing-Induced Atrial Electrical Remodeling in Rabbits

Cellular Physiology and Biochemistry

关键词: β3-adrenoceptor;    Atrial electrical remodeling;    L-type calcium current;    Inward rectifier potassium current;    Transient outward potassium current;   

DOI  :  10.1159/000331717

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Cardiac electrophysiological function is under the regulatory control of the sympathetic nervous system. In addition to classical β-adrenoceptors (β-AR, including β₁- and β₂- subtypes), β₃-AR is also expressed in human heart and shows its distinctive functions. This study is aimed to elucidate the role of β₃-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 β₃-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 β₃-AR agonist, leading to the increase of AF inducibility and duration. Similarly, β₃-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 β₃-AR antagonist, SR59230A. In summary, our study represents that activation of β₃-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 β₃-AR in heart diseases.

【 授权许可】

CC BY-NC-ND