© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation
Research Center, Department of Medicine, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec H1T 1C8, Canada
nattel{at}icm.umontreal.ca
* Corresponding author. Tel.: +1-514-376-3330; fax: +1-514-376-1355
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
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