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

Endocrinology. 2012 Mar;153(3):1269-78. doi: 10.1210/en.2011-1835. Epub 2012 Jan 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / metabolism*
  • Animals
  • Animals, Newborn
  • Apolipoprotein A-I / chemistry*
  • Calcium Channels, L-Type / chemistry*
  • Cells, Cultured
  • Dactinomycin / pharmacology
  • Electrophysiology / methods
  • Eplerenone
  • Immunoglobulin G / chemistry*
  • Myocytes, Cardiac / cytology
  • Oxidation-Reduction
  • Oxygen / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Mineralocorticoid / metabolism
  • Spironolactone / analogs & derivatives
  • Spironolactone / pharmacology
  • Time Factors


  • Apolipoprotein A-I
  • Calcium Channels, L-Type
  • Immunoglobulin G
  • Receptors, Mineralocorticoid
  • Dactinomycin
  • Spironolactone
  • Aldosterone
  • Eplerenone
  • Phosphatidylinositol 3-Kinases
  • Oxygen