title: Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation.
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 beta-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 beta-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 beta-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 beta-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.
authors.affiliation: Department of Medicine, Montreal Heart Institute, Quebec, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Gaspo
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: S
authors.initials: S
authors.lastname: Fareh
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: L
authors.initials: L
authors.lastname: Yue
authors.forename: B G
authors.initials: BG
authors.lastname: Allen
authors.forename: T E
authors.initials: TE
authors.lastname: Hebert
authors.forename: S
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D004095:Dihydropyridines / Q000378:metabolism*; D004285:Dogs; D005260:Female; D020120:Iodocyanopindolol / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D009568:Nitrendipine; D002118:Calcium