Baba Shigeo, Dun Wen, Hirose Masanori, Boyden Penelope A
Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY, USA.
Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H756-61. doi: 10.1152/ajpheart.00063.2006. Epub 2006 Apr 14.
The incidence of atrial fibrillation increases with age, but it is unknown whether there are changes in the intrinsic function of Na+ currents in cells of the aged atria. Thus, we studied right (RA) and left (LA) atrial cells from two groups of dogs, adult and aged (>8 yr), to determine the change in Na+ currents with age. In this study all dogs were in normal sinus rhythm. Whole cell voltage clamp techniques were used to compare the Na+ currents in the two cell groups. Immunocytochemical studies were completed for the Na+ channel protein Na(v)1.5 to determine whether there was structural remodeling of this protein with age. In cells from aged animals, we found that Na+ currents are similar to those we measured in adult atria. However, Na+ current (I(Na)) density of the aged atria differed depending on the atrial chamber with LA cell currents being larger than RA cell currents. Thus with age, the difference in I(Na) density between atrial chambers remains. I(Na) kinetic differences between aged and adult cells included a significant acceleration into the inactivated state and an enhanced use-dependent decrease in peak current in aged RA cells. Finally, there is no structural remodeling of the cardiac Na+ channel protein Na(v)1.5 in the aged atrial cell. In conclusion, with age there is no change in I(Na) density, but there are subtle kinetic differences contributing to slight enhancement of use dependence. There is no structural remodeling of the fast Na+ current protein with age.
心房颤动的发生率随年龄增长而增加，但老年心房细胞中钠电流的内在功能是否发生变化尚不清楚。因此，我们研究了两组犬（成年犬和老年犬（>8岁））的右心房（RA）和左心房（LA）细胞，以确定钠电流随年龄的变化。在本研究中，所有犬均处于正常窦性心律。采用全细胞膜片钳技术比较两组细胞中的钠电流。完成了针对钠通道蛋白Na(v)1.5的免疫细胞化学研究，以确定该蛋白是否随年龄发生结构重塑。在老年动物的细胞中，我们发现钠电流与我们在成年心房中测量的电流相似。然而，老年心房的钠电流（I(Na)）密度因心房腔不同而有所差异，左心房细胞电流大于右心房细胞电流。因此，随着年龄增长，心房腔之间I(Na)密度的差异仍然存在。老年细胞与成年细胞之间I(Na)动力学差异包括老年右心房细胞进入失活状态的显著加速以及峰值电流中使用依赖性降低的增强。最后，老年心房细胞中心脏钠通道蛋白Na(v)1.5没有结构重塑。总之，随着年龄增长，I(Na)密度没有变化，但存在细微的动力学差异，导致使用依赖性略有增强。快速钠电流蛋白不会随年龄发生结构重塑。
