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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria
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Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria

机译:老化对抗性动脉内皮钙信号传导和膜电位的影响:线粒体的作用

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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.
机译:老年期外周组织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,在内皮源性超极化(EDH)过程中,衰老是否会影响细胞内钙([Ca2+](i))信号与中小K+通道(SKCa/IKCa)活性之间的耦合尚不清楚,EDH是一种与血管阻力扩张相关的信号通路。为了探讨衰老对EDH的潜在影响,采用Fura-2光度法和细胞内记录法评估年轻(4-6个月)和老年(24-26个月)雄性C57BL/6小鼠上腹部动脉新鲜分离的完整内皮管(宽60μm;长1-3 mm)的[Ca2+]i和膜电位。作为对乙酰胆碱的反应,随着年龄的增长,内质网(ER)细胞内Ca2+的释放增强。此外,用线粒体解偶联剂FCCP治疗老年小鼠(而非年轻小鼠)的内皮细胞时,以SKCa/IKCa依赖的方式诱发[Ca2+]i的显著增加,并伴有膜超极化。我们的结论是,阻力动脉内皮细胞通过SKCa/IKCa激活从细胞内储存(即ER和线粒体)释放Ca2+和超极化V-m的能力增强,作为对老年期NO生物利用度降低的补偿。

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