Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators
Changlong Hu, … , Nick A. Guagliardo, Paula Q. Barrett
Changlong Hu, … , Nick A. Guagliardo, Paula Q. Barrett
Published May 1, 2012
Citation Information: J Clin Invest. 2012;122(6):2046-2053. https://doi.org/10.1172/JCI61996.
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Research Article Vascular biology

Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators

Abstract

Aldosterone, which plays a central role in the regulation of blood pressure, is produced by zona glomerulosa (ZG) cells of the adrenal gland. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and renal disease. Although sustained production of aldosterone requires persistent Ca2+ entry through low-voltage activated Ca2+ channels, isolated ZG cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca2+ entry. Here, we show that mouse ZG cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity. This innate electrical excitability of ZG cells provides a platform for the production of a recurrent Ca2+ signal that can be controlled by Ang II and extracellular potassium, the 2 major regulators of aldosterone production. We conclude that native ZG cells are electrical oscillators, and that this behavior provides what we believe to be a new molecular explanation for the control of Ca2+ entry in these steroidogenic cells.

Authors

Changlong Hu, Craig G. Rusin, Zhiyong Tan, Nick A. Guagliardo, Paula Q. Barrett

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Figure 4

External K+ and Ang II change ZG cell oscillatory behavior.

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External K+ and Ang II change ZG cell oscillatory behavior. Representa...
Representative current clamp recordings of ZG cells oscillating in standard buffer (3 mM K+) and after K+ substitution with 2 mM (A) or 5 mM (B) K+. Expanded traces are calculated average cycles from same voltage recordings. (C and D) Average oscillation frequency per cell (C) and average baseline Vm (D), calculated before and after hyperpolarization with 2 mM K+ (n = 5) or depolarization with 5 mM K+ (n = 5). (E) Representative current clamp recording of a cell spontaneously oscillating before and during exposure to 100 nM Ang II. Expanded traces are calculated average cycles from the same voltage recording. (F) Average oscillation frequency (calculated before and after exposure to a single concentration of Ang II), expressed as fold increase over the pre–Ang II frequency. Data points represent mean ± SEM and were fitted with a logistic equation. EC50 = 85.2 nM (n = 5 per concentration). *P < 0.05.