Ion Channel Function and Electrical Excitability in the Zona Glomerulosa: A Network Perspective on Aldosterone Regulation.
| Autor: | Barrett PQ; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA; email: pqb4b@virginia.edu, nag4g@virginia.edu, dab3y@virginia.edu., Guagliardo NA; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA; email: pqb4b@virginia.edu, nag4g@virginia.edu, dab3y@virginia.edu., Bayliss DA; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA; email: pqb4b@virginia.edu, nag4g@virginia.edu, dab3y@virginia.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Annual review of physiology [Annu Rev Physiol] 2021 Feb 10; Vol. 83, pp. 451-475. Date of Electronic Publication: 2020 Nov 11. |
| DOI: | 10.1146/annurev-physiol-030220-113038 |
| Abstrakt: | Aldosterone excess is a pathogenic factor in many hypertensive disorders. The discovery of numerous somatic and germline mutations in ion channels in primary hyperaldosteronism underscores the importance of plasma membrane conductances in determining the activation state of zona glomerulosa (zG) cells. Electrophysiological recordings describe an electrically quiescent behavior for dispersed zG cells. Yet, emerging data indicate that in native rosette structures in situ, zG cells are electrically excitable, generating slow periodic voltage spikes and coordinated bursts of Ca 2+ oscillations. We revisit data to understand how a multitude of conductances may underlie voltage/Ca 2+ oscillations, recognizing that zG layer self-renewal and cell heterogeneity may complicate this task. We review recent data to understand rosette architecture and apply maxims derived from computational network modeling to understand rosette function. The challenge going forward is to uncover how the rosette orchestrates the behavior of a functional network of conditional oscillators to control zG layer performance and aldosterone secretion. |
| Databáze: | MEDLINE |
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