Minireview: Aldosterone Biosynthesis: Electrically Gated for Our Protection

Abstract

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 Ca2+, and the sustained production of aldosterone depends on maintained Ca2+ 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 Ca2+ channels of the Cav3.x family, the major Ca2+ conductance on the ZG cell membrane. As a consequence, to activate sufficient Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ signal.