Journal Article

Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation

Rania Gaspo, Hui Sun, Samir Fareh, Mirie Levi, Lixia Yue, Bruce G. Allen, Terence E. Hebert and Stanley Nattel

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 42, issue 2, pages 434-442
Published in print May 1999 | ISSN: 0008-6363
Published online May 1999 | e-ISSN: 1755-3245 | DOI: https://dx.doi.org/10.1016/S0008-6363(99)00036-X
Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation

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Abstract

Background: We have shown that rapid atrial activation, as occurs during atrial fibrillation (AF), reduces L-type Ca2+ current (ICa) and that this is the principal mechanism of the action potential duration and refractoriness changes that characterize tachycardia-induced atrial remodeling. The present study was designed to determine whether atrial tachycardia alters biochemical indices of the number of L-type Ca2+ channels and/or of the number and binding affinity of β-adrenergic receptors. Methods: In canine atrial sarcolemmal preparations, the number and binding affinity of dihydropyridine receptors were determined with the use of 3H-nitrendipine and that of β-adrenergic receptors with 125I-iodocyanopindolol. Results were obtained with preparations from dogs paced at 400/min for 1 (P1, n=20), 7 (P7, n=9), and 42 (P42, n=9) days, and compared with observations in sham-operated controls (P0, n=14). Results: Pacing reduced the Bmax of dihydropyridine receptors, from 157±18 fmol/mg (P0) to 116±9 fmol/mg (P1, P <0.05), 100±14 fmol/mg (P7, P <0.05) and 94±9 fmol/mg (P42, P <0 .01). The affinity of dihydropyridine receptors was unchanged, with the Kd averaging 711±102 pM, 656±74 pM, 633±155 pM and 585±92 pM in P0, P1, P7 and P42 dogs. Neither Bmax nor Kd of β-adrenergic receptors was altered by rapid pacing. Values of Bmax of dihydropyridine receptors correlated with atrial ICa current density (r2=0.95) and ERP (r2=0.99). Conclusions: Rapid atrial activation results in downregulation in the number of dihydropyridine receptors without altering the number or affinity of β-adrenergic receptors. The reductions in ICa that play an important role in the atrial electrical remodeling by which ‘AF begets AF’ appear to be due at least in part to a decrease in the number of L-type Ca2+ channels in cardiac cell membranes.

Keywords: Atrial fibrillation; Beta-adrenergic receptors; Cardiac electrophysiology; Electrical remodeling; L-type calcium channels

Journal Article.  4477 words.  Illustrated.

Subjects: Cardiovascular Medicine

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