The mitochondrial Na super(+)/Ca super(2+) exchanger plays a key role in the control of cytosolic Ca super(2+) oscillations

• Published in: Cell calcium (Edinburgh) 2006-07, Vol.40 (1), p.53-61
• Main Authors: Hernandez-SanMiguel, Esther, Vay, Laura, Santo-Domingo, Jaime, Lobaton, Carmen D, Moreno, Alfredo, Montero, Mayte, Alvarez, Javier
• Format: Article
• Language: English
• ISSN: 0143-4160
• DOI: 10.1016/j.ceca.2006.03.009

There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca super(2+) signaling. We show here that the main mitochondrial Ca super(2+)-exit pathway, the mitochondrial Na super(+)/Ca super(2+) exchanger, controls the pattern of cytosolic Ca super(2+) oscillations in non-excitable cells. In HeLa cells, the inhibitor of the mitochondrial Na super(+)/Ca super(2+) exchanger CGP37157 changed the pattern of the oscillations induced by histamine from a high-frequency irregular one to a lower frequency baseline spike type, surprisingly with little changes in the average Ca super(2+) values of a large cell population. In human fibroblasts, CGP37157 increased the frequency of the baseline oscillations in cells having spontaneous activity and induced the generation of oscillations in cells without spontaneous activity. This effect was dose-dependent, disappeared when the inhibitor was washed out and was not mimicked by mitochondrial depolarization. CGP37157 increased mitochondrial [Ca super(2+)] and ATP production in histamine-stimulated HeLa cells, but the effect on ATP production was only transient. CGP37157 also activated histamine-induced Ca super(2+) release from the endoplasmic reticulum and increased the size of the cytosolic Ca super(2+) peak induced by histamine in HeLa cells. Our results suggest that the mitochondrial Na super(+)/Ca super(2+) exchanger directly modulates inositol 1,4,5-trisphosphate-induced Ca super(2+) release and in that way controls cytosolic Ca super(2+) oscillations.