Long-Term Modulation of Ion Channels by Aldosterone in Adult Rat Atrial Myocytes

Abstract

In recent years, both aldosterone and mineralocorticoid receptor (MR) have drawn attention as important factors that promote structural remodeling of the atrium. Here, we investigated effects of chronic aldosterone treatment on both intracellular Ca2+ and ion channels. Atrial myocytes were cultured in either the absence or presence of aldosterone, and then the activity of ion channels was studied, under whole-cell patch-clamp conditions. Aldosterone increased both the cell membrane capacitance (Cm) and the maximal conductance of ion channels that give rise to IKsus, INa, ICaT, and ICaL (30-100%). Except for inactivation curves of INa, which were shifted by −10 mV, aldosterone produced no major alterations in the biophysical properties of the channels. Interestingly, at resting membrane potentials the increase in INa was cancelled by a greater fraction of inactivation. The onset and recovery of the changes -in ICaT, ICaL, and Cm- were also assessed. In general, they required 2d to be noticeable, reached their maximal value in 6d, and returned to basal values after 1-3d of aldosterone removal. The effects on both Cm and ICaL were further studied -to explore both a potential dose-response relationship and a possible implication of the MR. In fact, co-incubating with 10 µM of spironolactone (an MR antagonist) abolished both effects. Furthermore, their corresponding magnitudes fitted well with the Hill equation, being the EC50 values for Cm and ICaL 20 and 130 (nM), respectively. Interestingly, aldosterone did not alter expression levels of Cav1.2, suggesting that the action on ICaL arises from a stimulus in open probability. The hormone also produced a 40% increase in the amplitude of Ca2+ transients along with a higher proportion of arrhythmic cells (2.5-fold increase). These results contribute to understanding the role of the MR and aldosterone in atrial electrophysiology.