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Cardiovascular Research 2003 58(3):526-534; doi:10.1016/S0008-6363(03)00288-8
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Calcium and potassium currents in cells from adult and aged canine right atria

Wen Dun1, Takuya Yagi1, Michael R Rosen and Penelope A Boyden*

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

pab4{at}columbia.edu

* Corresponding author. Present address: 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.

Background: Action potential (AP) contours vary considerably between normal adult and aged right atrial fibers. The ionic bases for these differences remain unknown. Therefore we studied Ca2+ and K+ currents in cells from adult and aged canine right atria (RA). Methods and Results: We used whole cell patch clamp recording techniques to measure L-type Ca2+ currents (ICaL) with either Ca2+ or Ba2+ (3 mM) as the charge carrier, and both the transient outward (Ito) and sustained potassium currents (Isus) in cells dispersed from normal adult (Adult, 2–5 years) and older dogs (Aged, >8 years). There is a significant reduction in peak ICaL (47%) and IBaL (43%) in Aged cells, yet differences in IBaL disappear with maximal β adrenergic stimulation (isoproterenol, 1 µM). Composite Ito and Isus densities were significantly increased in the Aged versus Adult cell group (by 31 and 27% at +50 mV, respectively). Ito decay during a maintained depolarization was slowed in Aged cells. Furthermore, Ito steady-state inactivation curve was shifted positively in Aged cells. Finally, composite Ito and Isus currents of Aged cells were more sensitive to tetraethylammonium chloride (TEA), a specific inhibitor of some types of K+ currents. In the presence of TEA (5 mM), Ito in Aged cells was significantly greater than that in Adult cells. Conclusions: Ionic currents differ in Aged versus Adult right atrial cells, such that a reduced Ca2+ current and augmented outward currents could contribute significantly to the altered AP contour of the Aged RA cell. Adrenergic stimulation appears to restore Ba2+ currents in Aged cells. Finally, an augmented TEA sensitive current plays a role in changes of Isus in Aged right atrial cells.

KEYWORDS Atria; Calcium current; Potassium currents; Cellular electrophysiology

1 These authors contributed equally to this work.


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