Mitochondria fine-tune the slow Ca2+ transients induced by electrical stimulation of skeletal myotubes

Veronica Eisner, Valentina Parra, Sergio Lavandero, Cecilia Hidalgo, Enrique Jaimovich

Producción científicarevisión exhaustiva

29 Citas (Scopus)

Resumen

Mitochondria sense cytoplasmic Ca2+ signals in many cell types. In mammalian skeletal myotubes, depolarizing stimuli induce two independent cytoplasmic Ca2+ signals: a fast signal associated with contraction and a slow signal that propagates to the nucleus and regulates gene expression. How mitochondria sense and possibly affect these cytoplasmic Ca2+ signals has not been reported. We investigated here (a) the emergence of mitochondrial Ca2+ signals in response to electrical stimulation of myotubes, (b) the contribution of mitochondrial Ca2+ transients to ATP generation and (c) the influence of mitochondria as modulators of cytoplasmic and nuclear Ca2+ signals. Rhod2 and Fluo3 fluorescence determinations revealed composite Ca2+ signals associated to the mitochondrial compartment in electrically stimulated (400 pulses, 45Hz) skeletal myotubes. Similar Ca2+ signals were detected when using a mitochondria-targeted pericam. The fast mitochondrial Ca2+ rise induced by stimulation was inhibited by pre-incubation with ryanodine, whereas the phospholipase C inhibitor U73122 blocked the slow mitochondrial Ca2+ signal, showing that mitochondria sense the two cytoplasmic Ca2+ signal components. The fast but not the slow Ca2+ transient enhanced mitochondrial ATP production. Inhibition of the mitochondrial Ca2+ uniporter prevented the emergence of mitochondrial Ca2+ transients and significantly increased the magnitude of slow cytoplasmic Ca2+ signals after stimulation. Precluding mitochondrial Ca2+ extrusion with the Na+/Ca2+ exchanger inhibitor CGP37157 decreased mitochondrial potential, increased the magnitude of the slow cytoplasmic Ca2+ signal and decreased the rate of Ca2+ signal propagation from one nucleus to the next. Over expression of the mitochondrial fission protein Drp-1 decreased mitochondrial size and the slow Ca2+ transient in mitochondria, but enhanced cytoplasmic and nuclear slow transients. The present results indicate that mitochondria play a central role in the regulation of Ca2+ signals involved in gene expression in myotubes.

Idioma originalEnglish
Páginas (desde-hasta)358-370
Número de páginas13
PublicaciónCell Calcium
Volumen48
N.º6
DOI
EstadoPublished - dic. 2010

Financiación

FinanciadoresNúmero del financiador
Fondo de Areas Prioritarias1080120, 3070043, 15010006
Comisión Nacional de Investigación Científica y Tecnológica
Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica
Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias

    ASJC Scopus Subject Areas

    • Physiology
    • Molecular Biology
    • Cell Biology

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    Citar esto

    Eisner, V., Parra, V., Lavandero, S., Hidalgo, C., & Jaimovich, E. (2010). Mitochondria fine-tune the slow Ca2+ transients induced by electrical stimulation of skeletal myotubes. Cell Calcium, 48(6), 358-370. https://doi.org/10.1016/j.ceca.2010.11.001