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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

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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 2

ZG cell oscillations depend on a Ni2+-sensitive current.

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ZG cell oscillations depend on a Ni2+-sensitive current.
 
Perfusion app...
Perfusion application of TTX to target Nav1.x, nifedipine to target Cav1.x, and Ni2+ to target Cav3.x. (A) Representative current clamp recording of a ZG cell stably oscillating 1 min before and during bath exposure to 60 μM TTX (rendering block of TTX-sensitive and insensitive Nav1 channels). Mean oscillation frequency of each of 9 cells before and after exposure to TTX at 100 nM (n = 5) or 60 μM (n = 4) is also shown. (B) Vm oscillations recorded before and during bath exposure to 1 μM nifedipine (NIF). Mean oscillation frequency of each recorded cell calculated before and after exposure to nifedepine at 100 nM (n = 4) or 1–3 μm (n = 3) is also shown. (C) Example of a cell with periods of rhythmic oscillations interrupted by intermittent periods of silence, before and after bath exposure to 50 μM Ni2+. Mean oscillation frequency was silenced by Ni2+ in all recorded cells (n = 6).

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