Chronic atrial fibrillation does not further decrease outward currents. It increases them.
Rapid atrial pacing causes electrical remodeling that leads to atrial fibrillation (AF). AF can further remodel atrial electrophysiology to maintain AF. Our previous studies showed that there was a marked difference in the duration of AF in dogs that have been atrial paced at 400 beats/min for 6 wk. We hypothesized that this difference is based on the changes in the degree of electrical remodeling caused by rapid atrial pacing versus that by AF. Right atrial cells were isolated from control dogs (Con, N = 28), from dogs with chronic AF (cAF dogs, N = 13, episodes lasting at least 6 days), or from dogs with nonsustained or brief episodes of AF (nAF dogs, N = 10, episodes lasting minutes to hours). Both transient outward (Ito) and sustained outward K+ current (Isus) densities/functions were determined using whole cell voltage-clamp techniques. In nAF cells, Ito density was reduced by 69% at +40 mV: from 7.1 +/- 0.5 pA/pF (Con, n = 59) to 2.2 +/- 0.2 pA/pF (nAF, n = 24) (P < 0.05). The voltage dependence of inactivation of Ito was shifted positively and decay kinetics were changed; however, recovery from inactivation was not altered in nAF cells. In contrast, Ito density in cAF cells was both significantly different from Con cells and larger than that in nAF cells [at +40 mV, 3.5 +/- 0.3 pA/pF (cAF, n = 29), P < 0.05]. In cAF cells, recovery from inactivation and decay of Ito were both slow; yet, voltage dependence inactivation of Ito approached that of Con cells. Furthermore, "recovered" Ito of cAF cells was more sensitive to tetraethylammonium than currents of Con and nAF cells. Isus densities of nAF and cAF cells did not differ. Both nAF and cAF cells have reduced Ito versus Con cells, but Ito remodeling of nAF cells differed from that of cAF cells. Ito in cAF dogs was likely remodeled by AF per se, whereas that in nAF dogs was likely the consequence of the rapid rate in the absence of sustained AF.
Dun
Wen
W
Department of Pharmacology, Center for Molecualr Therapeutics, Columbia College of Physicians and Surgeons, 630 W. 168th St., New York, NY 10032, USA.
Chandra
Parag
P
Danilo
Peter
P
Rosen
Michael R
MR
Boyden
Penelope A
PA
D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D002908:Chronic Disease; D004285:Dogs; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
D026902:Potassium Channel Blockers; D019789:Tetraethylammonium