Differential regulation of intracellular calcium oscillations by mitochondria and gap junctions

Bin Xian Zhang, Xiuye Ma, Zhenju Shu, Chih Ko Yeh, Russell H. Swerdlow, Michael S. Katz

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Fluctuations of intracellular Ca2+ ([Ca2+];) 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 [Ca 2+]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 [Ca 2+]i oscillations induced by GPCR and Tg are differentially modulated by mitochondria and gap junctions.

Original languageEnglish (US)
Pages (from-to)187-203
Number of pages17
JournalCell Biochemistry and Biophysics
Volume44
Issue number2
DOIs
StatePublished - Apr 2006

Keywords

  • Calcium oscillation
  • Gap junction
  • Intracellular ca
  • Mitochondria
  • p0 NT2 cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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