title: Role of voltage-gated calcium channels in the regulation of aldosterone production from zona glomerulosa cells of the adrenal cortex.
abstract: 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 Ca2+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 Ca2+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 Ca2+channels are assumed to provide the primary Ca2+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 CaV1.3 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 Ca2+signalling in ZG cells provides a unifying mechanism that explains how transiently activating CaV3.2 channels can generate a significant and recurring Ca2+signal, and how CaV1.3 channels may contribute to the Ca2+signal that drives aldosterone production.
authors: Department of Pharmacology, University of Virginia, Charlottesville, VA, 22947, USA.
authors: Paula Q
authors: PQ
authors: Barrett
authors: Department of Pharmacology, University of Virginia, Charlottesville, VA, 22947, USA.
authors: Nick A
authors: NA
authors: Guagliardo
authors: Department of Pharmacology, University of Virginia, Charlottesville, VA, 22947, USA.
authors: Peter M
authors: PM
authors: Klein
authors: Department of Physiology and Biophysics, School of Life Sciences, Institutes of Brain Science, Fudan University, Shanghai, 200433, China.
authors: Changlong
authors: C
authors: Hu
authors: Division of Endocrinology, Boston Children's Hospital, Boston, MA, 02115, USA.
authors: David T
authors: DT
authors: Breault
authors: Department of Pharmacology, University of Virginia, Charlottesville, VA, 22947, USA. mpb5y@virginia.edu.
authors: Mark P
authors: MP
authors: Beenhakker
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D006801:Humans; D015384:Zona Glomerulosa / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D000450:Aldosterone; D002118:Calcium