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Agonist‐induced mitochondrial Ca 2+ transients in smooth muscle
Author(s) -
Szado Tania,
Kuo KuoHsing,
BernardHelary Katy,
Poburko Damon,
Han Lee Cheng,
Seow Chun,
Ruegg Urs T.,
Breemen Cornelis
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0334com
Subject(s) - extracellular , endoplasmic reticulum , aequorin , mitochondrion , microbiology and biotechnology , organelle , chemistry , stimulation , intracellular , calcium , thapsigargin , serca , biophysics , uniporter , atpase , biology , biochemistry , cytosol , endocrinology , organic chemistry , enzyme
We investigated the role of mitochondria (MT) in calcium signaling in a culture of rat aortic smooth muscle cells. We used targeted aequorin to selectively measure [Ca 2 + ] in this organelle. Our results reveal that smooth muscle cell stimulation with agonists causes a large, transient increase in mitochondrial [Ca 2 + ] ([Ca 2 + ] m ). This large transient can be blocked with inhibitors of the sarco‐endoplasmic reticulum Ca 2 + ‐ATPase, suggesting a close relationship between the sarcoplasmic reticulum (SR) and the mitochondria. FCCP completely abolished the response to agonists, and targeted mitochondrial GFP revealed a vast tubular network of MT in these cells. When added before stimulation with ATP, IP 3 inhibitors partially blocked the ATP‐induced rise in mitochondrial Ca 2+ release. The role of the Na + /Ca 2+ exchanger (NCX) was examined by removing extracellular Na + . This procedure prevented the decrease in the [Ca 2 + ] m transient normally seen on removal of extracellular Ca 2 + . We propose a functional linkage of MT and SR dependent on a narrow junctional space between the two organelles in which Ca 2+ diffusion is restricted. Approximately half of the mitochondria appear to be associated with the superficial SR, which communicates with the extracellular space via NCX.—Szado, T., Kuo, K.‐H., Bernard‐Helary, K., Poburko, D., Lee, C. H., Seow, C., Ruegg, U. T., van Breemen, C. Agonist‐induced mitochondrial Ca 2+ transients in smooth muscle. FASEB J. 17, 28–37 (2003)