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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 Article has an altmetric score of 8

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 5

Vm oscillations increase Ca2+ entry carried by Cav3.2 channels.

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Vm oscillations increase Ca2+ entry carried by Cav3.2 channels.
 
(A) Vm...
(A) Vm oscillatory voltage commands generated from voltage recordings to construct average cycles (see Methods) that represent control and Ang II oscillatory activity. 4 (control; 2.14 s) or 8 (Ang II; 1.24 s) Vm cycles were delivered in 10 s (top traces). Mean Ca2+ currents evoked sequentially by control and Ang II voltage commands (n = 16) are shown below. Also displayed are magnified representations of the mean current elicited during first and last cycles. (B) Cycle comparison of averaged peak Ca2+ currents and averaged Ca2+ current areas. Peak current and current area per cycle per cell (n = 16) were calculated and averaged. Average Ca2+ current area summed across cycle number (i.e., total current) evoked by Ang II command was 240% that of control command. (C) Ni2+-sensitive Cav3.2 Ca2+ current. Mean Ca2+ currents recorded in the absence or presence of 100 μM Ni2+ evoked by the first or last Vm cycle. The blue difference current defines the Ni2+-sensitive Cav3.2 current, which, because of incomplete block by Ni2+, was an underestimate. (D) Average peak Ca2+ current and average Ca2+ current area compared between first and last cycle, showing persistent Ni2+ block (n = 6). Average Ni2+-sensitive component (Cav3.2) of Ca2+ current area summed across cycle number (i.e., total Ni2+-sensitive current) evoked by Ang II command was 220% that of control. (E) Mean Ni2+-sensitive current averaged during interspike intervals elicited by Ang II command (n = 6). +P < 0.05 vs. first cycle; *P < 0.05 vs. control. Bars represent mean ± SEM.

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

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