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

被引:53
作者
Dun, W
Yagi, T
Rosen, MR
Boyden, PA
机构
[1] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA
[2] Columbia Univ, Dept Pediat, Ctr Mol Therapeut, New York, NY 10032 USA
关键词
atria; calcium current; potassium currents; cellular electrophysiology;
D O I
10.1016/S0008-6363(03)00288-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (I-CaL) with either Ca2+ or Ba2+ (3 mM) as the charge carrier, and both the transient outward (I-to) and sustained potassium currents (I-sus) in cells dispersed from normal adult (Adult, 2-5 years) and older dogs (Aged, > 8 years). There is a significant reduction in peak I-CaL (47%) and I-BaL (43%) in Aged cells, yet differences in I-BaL disappear with maximal beta adrenergic stimulation (isoproterenol, 1 muM). Composite I-to and I-sus densities were significantly increased in the Aged versus Adult cell group (by 31 and 27% at +50 mV, respectively). I-to decay during a maintained depolarization was slowed in Aged cells. Furthermore, Ito steady-state inactivation curve was shifted positively in Aged cells. Finally, composite I-to and I-sus currents of Aged cells were more sensitive to tetraethyl ammonium chloride (TEA), a specific inhibitor of some types of K+ currents. In the presence of TEA (5 mM), It. 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 I-sus in Aged right atrial cells. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:526 / 534
页数:9
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