Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria
Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria
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DOI：
10.1093/gerona/glx079
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发表时间：
2017-12-01
影响因子：
5.1
通讯作者：
Segal, Steven S.
中科院分区：
文献类型：
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作者：
Behringer, Erik J.;Segal, Steven S.
在老年期间，外周组织的血流受损与内皮功能障碍和一氧化氮（NO）生物利用度降低有关。然而，目前尚不清楚衰老是否影响内皮源性超极化（EDH）过程中细胞内钙（[Ca 2 +]（i））信号传导与小和中等K+通道（SKCa/IKCa）活性之间的偶联，EDH是阻力血管扩张不可或缺的信号传导途径。为了解决衰老对EDH的潜在影响，应用Fura-2光度法和细胞内记录法来评估从年轻（4-6月龄）和老年（24-26月龄）雄性C57 BL/6小鼠的上级上腹动脉新鲜分离的完整内皮管（宽，60 μ m;长，1-3 mm）的[Ca 2 +] i和膜电位。在响应乙酰胆碱，胞内释放的Ca 2+从内质网（ER）的增强与老化。此外，与线粒体解偶联剂FCCP的治疗引起了显着增加[Ca 2 +] i与膜超极化在SKCa/IKCa依赖性的方式在老年人的内皮细胞，但不是年轻的小鼠。我们的结论是，阻力动脉内皮细胞释放Ca 2+从细胞内商店（即，ER和线粒体）和高血压V-m通过SKCa/IKCa激活的能力增强作为补偿减少NO生物利用度在高龄。
Impaired blood flow to peripheral tissues during advanced age is associated with endothelial dysfunction and diminished bioavailability of nitric oxide (NO). However, it is unknown whether aging impacts coupling between intracellular calcium ([Ca2+](i)) signaling and small-and intermediate K+ channel (SKCa/IKCa) activity during endothelium-derived hyperpolarization (EDH), a signaling pathway integral to dilation of the resistance vasculature. To address the potential impact of aging on EDH, Fura-2 photometry and intracellular recording were applied to evaluate [Ca2+] i and membrane potential of intact endothelial tubes (width, 60 mu m; length, 1-3 mm) freshly isolated from superior epigastric arteries of young (4-6 mo) and old (24-26 mo) male C57BL/6 mice. In response to acetylcholine, intracellular release of Ca2+ from the endoplasmic reticulum (ER) was enhanced with aging. Further, treatment with the mitochondrial uncoupler FCCP evoked a significant increase of [Ca2+] i with membrane hyperpolarization in an SKCa/IKCa-dependent manner in the endothelium of old but not young mice. We conclude that the ability of resistance artery endothelium to release Ca2+ from intracellular stores (ie, ER and mitochondria) and hyperpolarize V-m via SKCa/IKCa activation is augmented as compensation for reduced NO bioavailability during advanced age.