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Antiapolipoprotein A-1 IgG chronotropic effects require nongenomic action of aldosterone on L-type calcium channels

Publié dansEndocrinology, vol. 153, no. 3, p. 1269-1278
Date de publication2012
Résumé

Autoantibodies to apolipoprotein A-1 (antiapoA-1 IgG) have been shown to be associated with higher resting heart rate and morbidity in myocardial infarction patients and to behave as a chronotropic agent in the presence of aldosterone on isolated neonatal rat ventricular cardiomyocytes (NRVC). We aimed at identifying the pathways accounting for this aldosterone-dependent antiapoA-1 IgG-positive chronotropic effect on NRVC. The rate of regular spontaneous contractions was determined on NRVC in the presence of different steroid hormones and antagonists. AntiapoA-1 IgG chronotropic response was maximal within 20 min and observed only in aldosterone-pretreated cells but not in those exposed to other steroids. The positive antiapoA-1 IgG chronotropic effect was already significant after 5 min aldosterone preincubation, was dependent on 3-kinase and protein kinase A activities, was not inhibited by actinomycin D, and was fully abrogated by eplerenone (but not by spironolactone), demonstrating the dependence on a nongenomic action of aldosterone elicited through the mineralocorticoid receptor (MR). Under oxidative conditions (but not under normal redox state), corticosterone mimicked the permissive action of aldosterone on the antiapoA-1 IgG chronotropic response. Pharmacological and patch-clamp studies identified L-type calcium channels as crucial effectors of antiapoA-1 IgG chronotropic action, involving two converging pathways that increase the channel activity. The first one involves the rapid, nongenomic activation of the phosphatidylinositol 3-kinase enzyme by MR, and the second one requires a constitutive basal protein kinase A activity. In conclusion, our results indicate that, on NRVC, the aldosterone-dependent chronotropic effects of antiapoA-1 IgG involve the nongenomic activation of L-type calcium channels.

Mots-clés
  • Aldosterone/metabolism
  • Animals
  • Animals, Newborn
  • Apolipoprotein A-I/chemistry
  • Calcium Channels, L-Type/chemistry
  • Cells, Cultured
  • Dactinomycin/pharmacology
  • Electrophysiology/methods
  • Immunoglobulin G/chemistry
  • Myocytes, Cardiac/cytology
  • Oxidation-Reduction
  • Oxygen/chemistry
  • Phosphatidylinositol 3-Kinases/metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Mineralocorticoid/metabolism
  • Spironolactone/analogs & derivatives/pharmacology
  • Time Factors
Citation (format ISO)
ROSSIER, Michel et al. Antiapolipoprotein A-1 IgG chronotropic effects require nongenomic action of aldosterone on L-type calcium channels. In: Endocrinology, 2012, vol. 153, n° 3, p. 1269–1278. doi: 10.1210/en.2011-1835
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Article (Published version)
accessLevelRestricted
Identifiants
ISSN du journal0013-7227
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