Cytosolic calcium oscillations in human adrenocortical cells causing primary aldosteronism

Background Intracellular calcium [Ca2+]i is pivotal in driving aldosterone secretion. However, knowledge of the [Ca2+]i dynamics underlying aldosterone excess in primary aldosteronism (PA), the most common form of endocrine hypertension, is lacking due to the difficulty of obtaining aldosterone-producing adenoma (APA) cells ex vivo. Methods We used the Ca2+-sensitive Fura-2 dye and live confocal microscopy to investigate variations in [Ca2+]i under basal conditions and after angiotensin II (Ang II) stimulation in primary aldosterone-producing CD56+ cells, immunomagnetically isolated ex vivo from surgically treated PA patients. Results We found that the resting [Ca2+]i levels were consistently and markedly lower in APA cells (n = 14, 0.53; IQR: 0.33 - 0.79) compared with paired cells from the normal adjacent adrenal cortex (AAC) (n = 14, 0.80; IQR: 0.65 - 0.90, p = 0.021). While both cell types exhibited similar spontaneous oscillations, Ang II [1 nM] stimulation increased the number of cells exhibiting [Ca2+]i oscillations (p = 0.004) and induced a higher frequency of oscillations (p = 0.002) in APA than in AAC. Conclusion This study demonstrates prominent differences between APA and AAC cells in [Ca2+]i dynamics, with more marked oscillatory responses upon Ang II stimulation. These differences may underpin the increased aldosterone production, a hallmark of human PA.