Rapid atrial pacing at 400/min reduced the Bmax of dihydropyridine receptors from 157 fmol/mg in controls to 94 fmol/mg at 42 days (P<0.01), without altering beta-adrenergic receptors.
Does rapid atrial pacing alter the number and binding affinity of dihydropyridine and beta-adrenergic receptors in a canine model?
Rapid atrial activation downregulates the number of L-type Ca2+ channels, contributing to the electrical remodeling seen in atrial fibrillation.
Tasa de eventos absoluta: 94% vs 157%
valor p: p=<0.01
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.
Rania Gaspo (Sat,) conducted a other in Tachycardia-induced atrial fibrillation (n=52). Rapid atrial pacing vs. Sham-operated controls was evaluated on Bmax of dihydropyridine receptors (p=<0.01). Rapid atrial pacing at 400/min reduced the Bmax of dihydropyridine receptors from 157 fmol/mg in controls to 94 fmol/mg at 42 days (P<0.01), without altering beta-adrenergic receptors.