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Cardiovascular Research 2002 54(2):405-415; doi:10.1016/S0008-6363(02)00279-1
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Density and function of inward currents in right atrial cells from chronically fibrillating canine atria

Takuya Yagi, Jielin Pu1, Parag Chandra, Motoki Hara2, Peter Danilo, Jr., Michael R Rosen and Penelope A Boyden*

Departments of Pharmacology and Pediatrics, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA

* Corresponding author. Department of Pharmacology, Columbia College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032, USA. Tel.: +1-212-305-7907; Fax: +1-212-305-0529 pab4{at}columbia.edu

Objective: To determine whether INa and ICaL are altered in function/density in right atrial (RA) cells from dogs with chronic atrial fibrillation (cAF dogs, episodes lasting at least 6 days) and whether the changes that occur differ from those in dogs with nonsustained or brief episodes of fibrillation (nAF dogs). Methods: Using whole cell voltage clamp, sodium and calcium current density and function were determined in disaggregated RA cells from nAF, cAF and control atria (Con). Ca2+ currents were studied with either Ca2+ or Ba2+ as charge carrier, as well as with either EGTA or BAPTA as the internal solution Ca2+ chelator. Results: After rapid atrial pacing, dogs can either fibrillate for short periods of time (nAF) or longer, more sustained periods (cAF). Both the Na+ and Ca2+ current decrease in cells of the nAF atria. Na+ current density remains reduced in cAF cells with some slowing of recovery kinetics. Ca2+ current density does not further decrease with persistent atrial fibrillation (cAF cells) remaining significantly different from Con cells. However, the difference in density of Ca2+ currents between nAF and Con cells is negligible when Ba2+ is charge carrier and when Cai is quickly and effectively chelated with BAPTA. On the contrary, cAF IBaL densities remain significantly reduced compared to Con and nAF values when Ba2+/BAPTA conditions are used. Conclusions: Na+ current density/function does not recover to Con values in cAF. Further these enhanced Ca2+-dependent inactivation processes contribute significantly to the reduction of ICaL density observed in nAF cells while reduction of Ca2+ currents in cAF atria is probably by another mechanism

KEYWORDS Arrhythmia (mechanisms); Na-channel; Ca-channel; Remodeling; Supraventr. arrhythmia

2 Present address: Department of Medicine Keio University, Tokyo, Japan.

1 Present address: Department of Medicine University of Wisconsin, Madison, WI, USA.


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