Chronic atrial ionic remodeling by aldosterone: potentiation of L-type Ca2+ channels and its arrhythmogenic significance

  • Erick B. Ríos-Pérez
  • Maricela García-Castañeda
  • Adrián Monsalvo-Villegas
  • Guillermo AvilaEmail author
Ion channels, receptors and transporters


It is widely accepted that aldosterone induces atrial fibrillation (AF) by promoting structural changes, but its effects on the function of primary atrial myocytes remain unknown. We have investigated this point in adult rat atrial myocytes, chronically exposed to the hormone. This treatment produced larger amplitude of Ca2+ transients, longer action potential (AP) duration, and higher incidence of unsynchronized Ca2+ oscillations. Moreover, it also gave rise to increases in both cell membrane capacitance (Cm, 30 %) and activity of L-type Ca2+ channels (LTCCs, 100 %). Concerning K+ currents, a twofold increase was also observed, but only in a delayed rectifier component (IKsus). Interestingly, the maximal conductance (Gmax) of Na+ channels was also enhanced, but it occurred in the face of a negative shift in the voltage dependence of inactivation. Thus, at physiological potentials, a decreased fraction of available channels neutralized the effect on GNa-max. With regard to the effects on both Cm and LTCCs, they involved activation of mineralocorticoid receptors (MRs), were dose-dependent (EC50 ∼20–130 nM), and developed and recovered in days. Neither gating currents nor protein levels of LTCCs were altered. Instead, the effect on LTCCs was mimicked by cAMP, reverted by a PKA inhibitor, and attenuated by a nitric oxide donor (short-term exposures). Both EGTA and the antioxidant NAC prevented the increase in Cm, without significantly interfering with the upregulation of LTCCs. Overall, these results show that chronic exposures to aldosterone result in dire functional changes at the single myocyte level, which may explain the link between aldosteronism and AF.


Intracellular calcium Ion channels Cardiac myocyte EC coupling Mineralocorticoid receptor 



We would like to thank Marcelino Flores Flores for excellent technical assistance.

Compliance with ethical standards


This work was supported by a Conacyt grant to GA (no. 151540).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

424_2016_1876_MOESM1_ESM.docx (213 kb)
ESM 1 (DOCX 212 kb)


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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of BiochemistryCinvestav-IPNMéxico CityMéxico

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