Minireview: aldosterone biosynthesis: electrically gated for our protection.
Aldosterone produced by adrenal zona glomerulosa (ZG) cells plays an important role in maintaining salt/water balance and, hence, blood pressure homeostasis. However, when dysregulated, aldosterone advances renal and cardiovascular disease states. Multiple steps in the steroidogenic pathway require Ca(2+), and the sustained production of aldosterone depends on maintained Ca(2+) entry into the ZG cell. Nevertheless, the recorded membrane potential of isolated ZG cells is extremely hyperpolarized, allowing the opening of only a small fraction of low-voltage-activated Ca(2+) channels of the Ca(v)3.x family, the major Ca(2+) conductance on the ZG cell membrane. As a consequence, to activate sufficient Ca(2+) channels to sustain the production of aldosterone, aldosterone secretagogs would be required to affect large decreases in membrane voltage, a requirement that is inconsistent with the exquisite sensitivity of aldosterone production in vivo to small changes (0.1 mm) in extracellular K(+). In this review, we evaluate the contribution of membrane voltage and voltage-dependent Ca(2+) channels to the control of aldosterone production and consider data highlighting the electrical excitability of the ZG cell. This intrinsic capacity of ZG cells to behave as electrical oscillators provides a platform from which to generate a recurring Ca(2+) signal that is compatible with the lengthy time course of steroidogenesis and provides an alternative model for the physiological regulation of aldosterone production that permits both amplitude and temporal modulation of the Ca(2+) signal.
Department of Pharmacology, University of Virginia, P.O. Box 800735, Jordan Hall 5th Floor, 5058, Charlottesville, Virginia 22908, USA.
Nick A
NA
Guagliardo
Junlan
J
Yao
Changlong
C
Hu
Paula Q
PQ
Barrett
D000450:Aldosterone / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D006801:Humans; D015384:Zona Glomerulosa / Q000378:metabolism
D015220:Calcium Channels; D000450:Aldosterone; D002118:Calcium