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

Background: We have-shown that rapid atrial activation, as occurs during at rial fibrillation (AF), reduces L-type Ca2+ current (I-Ca) and that this is the principal mechanism of the action potential duration and refractorines s changes that characterize tachycardia-induced atrial remodeling. The pres ent study was designed to determine whether atrial tachycardia alters bioch emical indices of the number of L-type Ca2+ channels and/or of the number a nd binding affinity of beta-adrenergic receptors. Methods: In canine atrial sarcolemmal preparations, the number and binding affinity of dihydropyridi ne receptors were determined with the use of H-3-nitrendipine and that of b eta-adrenergic receptors with I-125-iodocyanopindolol. Results were obtaine d 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-operate d controls (P0, n=14). Results: Pacing reduced the B-max of dihydropyridine receptors, from 157+/-18 fmol/mg (P0) to 116+/-9 fmol/mg (P1, P <0.05), 10 0+/-14 fmol/mg (P7, P <0.05) and 94+/-9 fmol/mg (P42, P <0.01). The affinit y of dihydropyridine receptors was unchanged, with the K-d averaging 711+/- 102 pM, 656+/-74 pM. 633+/-155 pM and 585+/-92 pM in P0, P1, P7 and P42 dog s. Neither B-max nor K-d of beta-adrenergic receptors was altered by rapid pacing. Values of B-max of dihydropyridine receptors correlated with atrial I-Ca current density (r(2)=0.95) and ERP (r(2)=0.99). Conclusions: Rapid a trial activation results in downregulation in the number of dihydropyridine receptors without altering the number or affinity of beta-adrenergic recep tors. The reductions in I-Ca that play an important role in the atrial elec trical 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 membra nes. (C) 1999 Elsevier Science B.V. All rights reserved.