Tight mitochondrial control of calcium and exocytotic signals in chromaffin cells at embryonic life
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Calcium buffering by mitochondria plays a relevant physiological function in the regulation of Ca2+ and exocytotic signals in mature chromaffin cells (CCs) from various adult mammals. Whether a similar or different role of mitochondrial Ca2+ buffering is present in immature CCs at early life has not been explored. Here we present a comparative study in rat embryonic CCs and rat mother CCs, of various physiological parameters that are known to be affected by mitochondrial Ca2+ buffering during cell activation. We found that the clearance of cytosolic Ca2+ transients ([Ca2+]c) elicited by high K+ was 7-fold faster in embryo CCs compared to mother CCs. This strongly suggests that at embryonic life, the mitochondria play a more significant role in the clearance of [Ca2+]c loads compared to adult life. Consistent with this view are the following results concerning the transient suppression of mitochondrial Ca2+ buffering by protonophore FCCP, in embryonic CCs compared to mother CCs: (i) faster and greater inactivation of inward calcium currents, (ii) higher K+-elicited [Ca2+]c transients with 25-fold faster clearance, (iii) higher increase of basal catecholamine release and (iv) higher potentiation of K+-evoked secretion. These pronounced differences could be explained by two additional features (embryo versus mother CCs): (a) slower recovery of mitochondrial resting membrane potential after the application of a transient FCCP pulse and (b) greater relative density of the mitochondria in the cytosol. This tighter control by the mitochondria of Ca2+ and exocytotic signals may be relevant to secure a healthy catecholamine secretory response at early life.
KeywordsChromaffin cells Embryo chromaffin cells Mitochondria Calcium Calcium channels
Cytosolic Ca2+ concentrations
Mitochondrial Ca2+ concentrations
Voltage-activated calcium channels
We want to express our gratitude to Professor Luis Santamaría-Solís (Department of Anatomy, Histology, and Neuroscience, School of Medicine, University Autónoma of Madrid) for helping us with the data analysis of EM imaging. This work was supported by the following grants to AGG: (1) SAF 2010–21795 and (2) SAF 2013–44108, Ministerio de Economía y Competitividad, Spain; (3) CABICYC, UAM/Bioibérica, Spain; and (4) the continued support of Fundación Teófilo Hernando, Madrid, Spain.
Antonio G. García, Antonio-Miguel G. de Diego, Juan-Fernando Padín and José-Carlos Fernández-Morales participated in the research design; Stefan Vestring, José-Carlos Fernández-Morales, Antonio-Miguel G. de Diego, Juan-Fernando Padín, Diego Castro-Musial and Iago Méndez-López conducted the experiments; José-Carlos Fernández-Morales, Stefan Vestring, Juan-Fernando Padín and Iago Méndez-López performed the data analysis; and Antonio G. García and Juan-Fernando Padín wrote or contributed to the writing of the manuscript.
Conflict of interest
The authors declare that they have no competing interests.
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