Role of voltage‐gated calcium channels in the regulation of aldosterone production from zona glomerulosa cells of the adrenal cortex
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- 作者：Paula Q. Barrett ; Nick A. Guagliardo ; Peter M. Klein ; Changlong Hu ; David T. Breault ; Mark P. Beenhakker
- 刊名：The Journal of Physiology
- 出版年：2016
- 出版时间：15 October 2016
- 年：2016
- 卷：594
- 期：20
- 页码：5851-5860
- 全文大小：403.2KB
- ISSN：1469-7793
文摘
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 Cap>2+ p> 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 Cap>2+ p> 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 Cap>2+ p> channels are assumed to provide the primary Cap>2+ p> 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 Cap>2+ p> signalling in ZG cells provides a unifying mechanism that explains how transiently activating CaV3.2 channels can generate a significant and recurring Cap>2+ p> signal, and how CaV1.3 channels may contribute to the Cap>2+ p> signal that drives aldosterone production.