Declining into failure - The age-dependent loss of the L-type calcium channel within the sinoatrial node
Declining into failure - The age-dependent loss of the L-type calcium channel within the sinoatrial node
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DOI：
10.1161/circulationaha.106.663070
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发表时间：
2007-03-13
期刊：
影响因子：
37.8
通讯作者：
Lancaster, Matthew K.
中科院分区：
文献类型：
--
作者：
Jones, Sandra A.;Boyett, Mark R.;Lancaster, Matthew K.
正常生理条件下，窦房结起搏细胞的自发活动控制心率。临床研究表明，SA结功能障碍的发生率随年龄增长而增加，并在老年人群中达到高峰。本研究调查是否老化影响的Ca（V）1.2通道的表达，这些变化是否会影响起搏器的活动，反过来导致与年龄相关的SA结degeneration.Methods和Results-SA结区域被隔离从出生和38个月的年龄之间的豚鼠的右心房。免疫荧光显示Ca（v）1.2蛋白在心房细胞外膜周围呈点状标记，而在窦房结中央未见。缺乏Ca（v）1.2标记蛋白的区域从1个月时的2.06 +/-0.1（平均值+/-SEM）mm（2）逐渐增加到38个月时的18.72 +/-2.2 mm（2）（P <0.001）。Western blot证实SA结内Ca（v）1.2蛋白表达在衰老过程中下降。功能测量结果表明，增加的敏感性L-型钙阻滞剂硝苯地平; SA节点准备停止跳动在100 μ mol/L硝苯地平在1日龄，相比之下，30 μ mol/L在1个月和10 μ mol/L在38个月的年龄。此外，细胞外电位的幅度下降的中心和周边的SA node.Conclusions-目前的数据显示，Ca（V）1.2通道蛋白减少，同时减少自发活动的SA节点随着年龄的增加，这提供了进一步的证据的机制与年龄相关的恶化的心脏起搏器。
Background - The spontaneous activity of pacemaker cells in the sinoatrial (SA) node controls heart rate under normal physiological conditions. Clinical studies have shown the incidence of SA node dysfunction increases with age and occurs with peak prevalence in the elderly population. The present study investigated whether aging affected the expression of Ca(v)1.2 channels and whether these changes could affect pacemaker activity, in turn leading to age-related SA node degeneration.Methods and Results - The SA node region was isolated from the right atrium of guinea pigs between birth and 38 months of age. Immunofluorescence studies showed Ca(v)1.2 protein was present as punctate labeling around the outer membrane of atrial cells but was absent from the center of the SA node. The area lacking Ca(v)1.2-labeled protein progressively increased from 2.06 +/- 0.1 (mean +/- SEM) mm(2) at 1 month to 18.72 +/- 2.2 mm(2) at 38 months (P < 0.001). Western blot provided verification that Ca(v)1.2 protein expression within the SA node declined during aging. Functional measurements showed an increased sensitivity to the L-type calcium blocker nifedipine; SA node preparations stopped beating in 100 mu mol/L nifedipine at 1 day old, compared with 30 mu mol/L at 1 month and 10 mu mol/L at 38 months of age. Furthermore, the amplitude of extracellular potentials declined within the center and periphery of the SA node during aging.Conclusions - The present data show Ca(v)1.2 channel protein decreases concurrently with reduced spontaneous activity of the SA node with increased age, which provides further evidence of mechanisms underlying the age-related deterioration of the cardiac pacemaker.