L- and T-type calcium channels control aldosterone production from human adrenals. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Yang, Tingting; He, Min; Zhang, Hailiang; Barrett, Paula Q; Hu, Changlong
• Is Part Of: Journal of endocrinology. Volume 244:Issue 1(2020)
• Page Start: 237
• Page End: 247
• Publication Date: 2020-01
• Subjects: T-type calcium channels -- L-type calcium channels -- aldosterone secretion -- primary aldosteronism; Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/JOE-19-0259
• Languages: English
• ISSNs: 0022-0795

Abstract

Abstract : Aldosterone, which plays a key role in the regulation of blood pressure, is produced by zona glomerulosa (ZG) cells of the adrenal cortex. Exaggerated overproduction of aldosterone from ZG cells causes primary hyperaldosteronism. In ZG cells, calcium entry through voltage-gated calcium channels plays a central role in the regulation of aldosterone secretion. Previous studies in animal adrenals and human adrenal adrenocortical cell lines suggest that the T-type but not the L-type calcium channel activity drives aldosterone production. However, recent clinical studies show that somatic mutations in L-type calcium channels are the second most prevalent cause of aldosterone-producing adenoma. Our objective was to define the roles of T and L-type calcium channels in regulating aldosterone secretion from human adrenals. We find that human adrenal ZG cells mainly express T-type CaV 3.2/3.3 and L-type CaV 1.2/1.3 calcium channels. TTA-P2, a specific inhibitor of T-type calcium channel subtypes, reduced basal aldosterone secretion from acutely prepared slices of human adrenals. Surprisingly, nifedipine, the prototypic inhibitor of L-type calcium channels, also decreased basal aldosterone secretion, suggesting that L-type calcium channels are active under basal conditions. In addition, TTA-P2 or nifedipine also inhibited aldosterone secretion stimulated by angiotensin II- or elevations in extracellular K + . Remarkably, blockade of either L- or T-type calcium channels inhibits basal and stimulated aldosterone production to a similar extent. Low concentrations of TTA-P2 and nifedipine showed additive inhibitory effect on aldosterone secretion. We conclude that T- and L-type calcium channels play equally important roles in controlling aldosterone production from human adrenals.