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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 3

ZG Ca2+ currents are robust and Cav3.2-like.

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ZG Ca2+ currents are robust and Cav3.2-like.
 
(A) Ca2+ currents evoked ...
(A) Ca2+ currents evoked by 100-ms steps from –70 to +40 mV in 10-mV increments applied every 6 s from a VH of –90 or –50 mV. Shown are representative currents evoked by steps to –60, –40, or +10 mV from a VH of –90 or –50 mV to reduce Cav3.x channel availability. Current-voltage relationship was constructed from peak current densities (n = 16). (B) Representative currents as in A evoked in the presence of 1 μM (S)-(–)BAYK8644 or 1 μM nifedipine from a VH of –90 mV. Current-voltage relationships were constructed from peak current densities (n = 8 per group). (C) Ca2+ currents evoked by step (100-ms to –40 mV) or tail current (35-ms repolarization to –70 mV following 9-ms step to –40 mV) voltage protocols from a VH of –90 mV applied every 6 s, in the absence, then presence, of Ni2+ in the bath solution from 1 to 100 μM (mean ± SEM). (D) Ni2+ inhibition curves of Ca2+ channel currents (ICa). Percent inhibition was calculated as measured current relative to maximal current recorded in the absence of Ni2+. Datasets were fitted with a logistic equation yielding IC50 22.5 μM (n = 6) for Ni2+ block of Ca2+ currents expressed in ZG cells and 9.2 μM (n = 6) for block of recombinant Cav3.2 currents expressed in HEK293 cells.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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