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Differential regulation of intracellular calcium oscillations by mitochondria and gap junctions

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An Erratum to this article was published on 01 May 2006

Abstract

Fluctuations of intracellular Ca2+ ([Ca2+]i) regulate a variety of cellular functions. The classical Ca2+ transport pathways in the endoplasmic reticulum (ER) and plasma membrane are essential to [Ca2+]i oscillations. Although mitochondria have recently been shown to absorb and release Ca2+ during G protein-coupled receptor (GPCR) activation, the role of mitochondria in [Ca2+]i oscillations remains to be elucidated. Using fluo-3-loaded human teratocarcinoma NT2 cells, we investigated the regulation of [Ca2+]i oscillations by mitochondria. Both the muscarinic GPCR agonist carbachol and the ER Ca2+-adenosine triphosphate inhibitor thapsigargin (Tg) induced [Ca2+]i oscillations in NT2 cells. The [Ca2+]i oscillations induced by carbachol were unsynchronized among individual NT2 cells; in contrast, Tg-induced oscillations were synchronized. Inhibition of mitochondrial functions with either mitochondrial blockers or depletion of mitochondrial DNA eliminated carbachol—but not Tg-induced [Ca2+]i oscillations. Furthermore, carbachol-induced [Ca2+]i oscillations were partially restored to mitochondrial DNA-depleted NT2 cells by introduction of exogenous mitochondria. Treatment of NT2 cells with gap junction blockers prevented Tg-induced but not carbachol-induced [Ca2+]i oscillations. These data suggest that the distinct patterns of [Ca2+]i oscillations induced by GPCR and Tg are differentially modulated by mitochondria and gap junctions.

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Authors and Affiliations

  1. Geriatric Research, Education and Clinical Center (182), Audie L. Murphy Division, South Texas Veterans Health Care System, 7400 Merton Minter Boulevard, 78229, San Antonio, TX

    Bin-Xian Zhang, Chih-Ko Yeh & Michael S. Katz

  2. Department of Medicine, University of Texas Health Science Center at San Antonio, 78229, San Antonio, TX

    Bin-Xian Zhang, Zhenju Shu & Michael S. Katz

  3. Department of Biochemistry, University of Texas Health Science Center at San Antonio, 78229, San Antonio, TX

    Xiuye Ma

  4. Department of Dental Diagnostic Science, University of Texas Health Science Center at San Antonio, 78229, San Antonio, TX

    Chih-Ko Yeh

  5. Department of Neurology, University of Virginia Health Sciences Center, 22908, Charlottesville, VA

    Russell H. Swerdlow

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  1. Bin-Xian Zhang
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  2. Xiuye Ma
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Correspondence to Bin-Xian Zhang.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1385/CBB:45:1:125.

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Zhang, BX., Ma, X., Shu, Z. et al. Differential regulation of intracellular calcium oscillations by mitochondria and gap junctions. Cell Biochem Biophys 44, 187–203 (2006). https://doi.org/10.1385/CBB:44:2:187

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