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首页> 外文期刊>The FASEB Journal >Pancreatic β-cell Na+ channels control global Ca 2+ signaling and oxidative metabolism by inducing Na+and Ca2+ responses that are propagated into mitochondria
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Pancreatic β-cell Na+ channels control global Ca 2+ signaling and oxidative metabolism by inducing Na+and Ca2+ responses that are propagated into mitochondria

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摘要

Communication between the plasma membrane and mitochondria is essential for initiating the Ca2+ and metabolic signals required for secretion in β cells. Although voltage-dependent Na+ channels are abundantly expressed in β cells and activated by glucose, their role in communicating with mitochondria is unresolved. Here, we combined fluorescent Na+, Ca2+, and ATP imaging, electrophysiological analysis with tetrodotoxin (TTX)-dependent block of the Na+ channel, and molecular manipulation of mitochondrial Ca2+ transporters to study the communication between Na+ channels and mitochondria. We show that TTX inhibits glucose-dependent depolarization and blocks cytosolic Na+ and Ca2+ responses and their propagation into mitochondria. TTX-sensitive mitochondrial Ca2+ influx was largely blocked by knockdown of the mitochondrial Ca2+ uniporter (MCU) expression. Knockdown of the mitochondrial Na+/Ca2+ exchanger (NCLX) and Na+ dose response analysis demonstrated that NCLX mediates the mitochondrial Na+ influx and is tuned to sense the TTX-sensitive cytosolic Na+ responses. Finally, TTX blocked glucose-dependent mitochondrial Ca2+ rise, mitochondrial metabolic activity, and ATP production. Our results show that communication of the Na+ channels with mitochondria shape both global Ca2+ and metabolism signals linked to insulin secretion in β cells.

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  • 来源
    《The FASEB Journal》 |2014年第8期|3301-3312|共12页
  • 作者

    NitaI.I.; HershfinkelM.; KantorC.RutterG.A.LewisE.C.SeklerI.;

  • 作者单位

    Department of Medicine, Faculty of Medicine, Imperial College London, London, United Kingdom;

    Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev;

    Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the;

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  • 原文格式 PDF
  • 正文语种 英语
  • 中图分类 生物化学;
  • 关键词

    MCU; NCLX; TTX;

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