Differential regulation of intracellular calcium oscillations by mitochondria and gap junctions.
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.
Zhang
Bin-Xian
BX
Geriatric Research, Education and Clinical Center (182), Audie L. Murphy Division, South Texas Veterans Health Care System, 7400 Merton Minter Boulevard, San Antonio, TX 78229, USA. binxz@yahoo.com
Ma
Xiuye
X
Shu
Zhenju
Z
Yeh
Chih-Ko
CK
Swerdlow
Russell H
RH
Katz
Michael S
MS
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D018243:Teratocarcinoma / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D043562:Receptors, G-Protein-Coupled; D019284:Thapsigargin; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D002118:Calcium