title: Tight mitochondrial control of calcium and exocytotic signals in chromaffin cells at embryonic life.
abstract: Calcium buffering by mitochondria plays a relevant physiological function in the regulation of Ca(2+) and exocytotic signals in mature chromaffin cells (CCs) from various adult mammals. Whether a similar or different role of mitochondrial Ca(2+) 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 Ca(2+) buffering during cell activation. We found that the clearance of cytosolic Ca(2+) transients ([Ca(2+)]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 [Ca(2+)]c loads compared to adult life. Consistent with this view are the following results concerning the transient suppression of mitochondrial Ca(2+) buffering by protonophore FCCP, in embryonic CCs compared to mother CCs: (i) faster and greater inactivation of inward calcium currents, (ii) higher K(+)-elicited [Ca(2+)]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 Ca(2+) and exocytotic signals may be relevant to secure a healthy catecholamine secretory response at early life.
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029, Madrid, Spain.|Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vestring
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Avda. Arzobispo Morcillo, 4, 28029, Madrid, Spain.
authors.forename: José C
authors.initials: JC
authors.lastname: Fernández-Morales
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Avda. Arzobispo Morcillo, 4, 28029, Madrid, Spain.
authors.forename: Iago
authors.initials: I
authors.lastname: Méndez-López
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Avda. Arzobispo Morcillo, 4, 28029, Madrid, Spain.|Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: C Musial
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Avda. Arzobispo Morcillo, 4, 28029, Madrid, Spain.
authors.forename: Antonio-Miguel
authors.initials: AM
authors.lastname: G de Diego
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Avda. Arzobispo Morcillo, 4, 28029, Madrid, Spain.
authors.forename: J Fernando
authors.initials: JF
authors.lastname: Padín
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029, Madrid, Spain. agg@uam.es.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Avda. Arzobispo Morcillo, 4, 28029, Madrid, Spain. agg@uam.es.|Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, UAM, Madrid, Spain. agg@uam.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: G García
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling; D002395:Catecholamines / Q000494:pharmacology; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002395:Catecholamines
keywords: Calcium; Calcium channels; Chromaffin cells; Embryo chromaffin cells; Mitochondria