Under-expression of the TWIK-related acid-sensitive K+ channel 2 (TASK-2) gene is a hallmark of aldosterone producing adenoma causing human primary aldosteronism
Livia Lenzini1, Teresa Maria Seccia1, Brasilina Caroccia1, Chiara Recarti1, Maria Rosa Pelizzo2 & GianPaolo Rossi1
Background: Primary aldosteronism is a common cause of arterial hypertension, but its underlying molecular mechanisms are unknown. K+ is a key regulator of aldosterone secretion: it interacts with physiological secretagogues of aldosterone as angiotensin II (Ang II) end endothelin-1. In vivo genetic manipulation of a widely distributed class of channels, which generate background or leak potassium (K+) currents, the twik-related acid-sensitive K channel 1 (TASK-1) and 3 (TASK-3), resulted in a phenotype which closely mimics human primary aldosteronism.
Objective: To investigate the expression of the K+ channels of the TASK family in a series of aldosterone producing adenoma (APA).
Results: The most expressed TASK channel gene in both the normal ZG and in APAs was TASK-1, followed by TASK-2 while the expression of TSAK-3 was scant. With a whole transcriptome analysis followed by confirmation with quantitative real time RT-PCR we found a consistent and marked under expression of TASK-2 channel in all studied APA (n=24), while TASK-1 and TASK-3 were heterogeneously expressed, as compared to the normal adrenal cortex. Immunohistochemistry was used to confirm the expression of the 3 TASK K+ chennels in the adrenal cortex at the protein level and quantitative immnunoblotting will be used to confirm the differences detected at the transcript level.
Conclusions: These results suggest that a blunted activity of TASK-2 results into lowering the membrane potential and thereby in opening of the voltage-gated T-type calcium channels, thus rendering zona glomerulosa cells more sensitive to aldosterone secretagogues. These ex vivo findings, while pointing to TASK-2 channels under-expression as an important role in the pathophysiology of primary aldosteronism, mandates further studies to conclusively establish their functional relevance.