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

Maturana, Andres D
Published in Endocrinology. 2012, vol. 153, no. 3, p. 1269-78
Abstract 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.
Keywords Aldosterone/metabolismAnimalsAnimals, NewbornApolipoprotein A-I/chemistryCalcium Channels, L-Type/chemistryCells, CulturedDactinomycin/pharmacologyElectrophysiology/methodsImmunoglobulin G/chemistryMyocytes, Cardiac/cytologyOxidation-ReductionOxygen/chemistryPhosphatidylinositol 3-Kinases/metabolismRatsRats, WistarReceptors, Mineralocorticoid/metabolismSpironolactone/analogs & derivatives/pharmacologyTime Factors
PMID: 22253414
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Research groups Etude de l'activation des monocytes/macrophages et des polynucléaires neutrophiles (779)
Chimie et protéomique clinique (270)
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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. 1269-78. https://archive-ouverte.unige.ch/unige:27587

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Deposited on : 2013-04-26

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