Abstract
Aldosterone-producing zona glomerulosa (zG) cells of the adrenal gland arrange in distinct multi-cellular rosettes that provide a structural framework for adrenal cortex morphogenesis and plasticity. Whether this cyto-architecture also plays functional roles in signaling remains unexplored. To determine if structure informs function, we generated mice with zG-specific expression of GCaMP3 and imaged zG cells within their native rosette structure. Here we demonstrate that within the rosette, angiotensin II evokes periodic Cav3-dependent calcium events that form bursts that are stereotypic in form. Our data reveal a critical role for angiotensin II in regulating burst occurrence, and a multifunctional role for the rosette structure in activity-prolongation and coordination. Combined our data define the calcium burst as the fundamental unit of zG layer activity evoked by angiotensin II and highlight a novel role for the rosette as a facilitator of cell communication.
Highlights
Aldosterone-producing zona glomerulosa cells of the adrenal gland arrange in distinct multi-cellular rosettes that provide a structural framework for adrenal cortex morphogenesis and plasticity
Mice in which Cre recombinase was targeted to the Cyp11b2 (AS, aldosterone synthase) genomic locus[4] were crossed with floxed GCaMP3 mice to generate a mouse line (ASCre/+::ROSA26floxGCaMP3/HZE, zona glomerulosa (zG)-GCaMP3) in which GCaMP3 was targeted to zG cells
We demonstrate that zG cells situated within their native rosettes produce robust, sustained calcium oscillations in response to the primary regulator of aldosterone production, Ang II
Summary
Aldosterone-producing zona glomerulosa (zG) cells of the adrenal gland arrange in distinct multi-cellular rosettes that provide a structural framework for adrenal cortex morphogenesis and plasticity Whether this cyto-architecture plays functional roles in signaling remains unexplored. We previously demonstrated by patch-clamp electrophysiology that cells within the mouse zG layer produce robust and prolonged voltage oscillations[22] that can drive rhythmic calcium currents These data confirmed and extended previous findings obtained by sharp electrode recordings of feline adrenal slices[23] and are in agreement with oscillatory calcium activity previously observed in slices[24]. We find that Ang II, the major regulator of aldosterone production from the zG layer, elicits stereotypic oscillatory zG cell calcium bursts whose occurrence is concentration dependent This dependence does not manifest as a simple change in oscillation frequency as is primarily observed with autonomous electrical oscillators. We provide evidence for the hypothesis that the adrenal rosette, a dynamic multi-cellular arrangement of zG cells, functions as a network oscillator in which constituent cells communicate to produce bursts of activity that are coordinated
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