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1 Department of Pharmacology, Columbia University, NY, NY, USA
2 Department of Pharmacology, Columbia University, NY, NY, USA; Department of Pediatrics, Columbia University, NY, NY, USA
* To whom correspondence should be addressed. E-mail: pab4{at}columbia.edu.
Backgroud 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 bpm for 6 weeks. 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. Methods and Results Right atrial cells were isolated from control dogs (Con, N=28) from dogs with chronic atrial fibrillation (cAF dogs, N=13, episodes lasting at least 6 days) or those with nonsustained or brief episodes of fibrillation (nAF dogs, N=10, episodes lasting minutes to hours). Both the transient (Ito) and the sustained outward (Isus) current 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, 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. Further, "recovered" Ito of cAF cells was more sensitive to tetraethylammonium (TEA) than currents of Con and nAF cells. Isus densities of nAF and cAF did not differ. Conclusion nAF and cAF cells both have reduced Ito versus Con, but Ito remodeling of nAF differed from that of cAF cells. Ito in cAF dogs was likely remodeled by AF per se while that in nAF dogs was likely the consequence of the rapid rate in the absence of sustained AF.
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