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Role of voltage‐gated calcium channels in the regulation of aldosterone production from zona glomerulosa cells of the adrenal cortex
Author(s) -
Barrett Paula Q.,
Guagliardo Nick A.,
Klein Peter M.,
Hu Changlong,
Breault David T.,
Beenhakker Mark P.
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp271896
Subject(s) - zona glomerulosa , aldosterone , adrenal cortex , endocrinology , medicine , calcium , voltage dependent calcium channel , biology , neuroscience , receptor , angiotensin ii
Zona glomerulosa cells (ZG) of the adrenal gland constantly integrate fluctuating ionic, hormonal and paracrine signals to control the synthesis and secretion of aldosterone. These signals modulate Ca 2+ levels, which provide the critical second messenger to drive steroid hormone production. Angiotensin II is a hormone known to modulate the activity of voltage‐dependent L‐ and T‐type Ca 2+ channels that are expressed on the plasma membrane of ZG cells in many species. Because the ZG cell maintains a resting membrane voltage of approximately −85 mV and has been considered electrically silent, low voltage‐activated T‐type Ca 2+ channels are assumed to provide the primary Ca 2+ signal that drives aldosterone production. However, this view has recently been challenged by human genetic studies identifying somatic gain‐of‐function mutations in L‐type Ca V 1.3 channels in aldosterone‐producing adenomas of patients with primary hyperaldosteronism. We provide a review of these assumptions and challenges, and update our understanding of the state of the ZG cell in a layer in which native cellular associations are preserved. This updated view of Ca 2+ signalling in ZG cells provides a unifying mechanism that explains how transiently activating Ca V 3.2 channels can generate a significant and recurring Ca 2+ signal, and how Ca V 1.3 channels may contribute to the Ca 2+ signal that drives aldosterone production.