Cholinergic and peptidergic neurotransmission in the adrenal medulla: A dynamic control of stimulus‐secretion coupling

Guérineau, Nathalie C.

doi:10.1002/iub.2117

Cited by 24 publications

(26 citation statements)

References 139 publications

(251 reference statements)

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“…Adrenomedullary chromaffin cells serve as a key effector arm of the sympathetic nervous system. In response to stimulation by preganglionic sympathetic nerves, they secrete a number of important hormones, including epinephrine, norepinephrine, neuropeptide Y (NPY), and tissue plasminogen activator (tPA) directly into the circulation (Carmichael & Winkler, 1985; Guerineau, 2019). The trigger for stimulus‐evoked exocytosis in adrenal chromaffin cells is a rise in intracellular Ca 2+ .…”

Section: Introductionmentioning

confidence: 99%

Synaptotagmin‐7 enhances calcium‐sensing of chromaffin cell granules and slows discharge of granule cargos

Bendahmane

Morales

Kreutzberger

et al. 2020

Journal of Neurochemistry

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Synaptotagmin‐7 (Syt‐7) is one of two major calcium sensors for exocytosis in adrenal chromaffin cells, the other being synaptotagmin‐1 (Syt‐1). Despite a broad appreciation for the importance of Syt‐7, questions remain as to its localization, function in mediating discharge of dense core granule cargos, and role in triggering release in response to physiological stimulation. These questions were addressed using two distinct experimental preparations—mouse chromaffin cells lacking endogenous Syt‐7 (KO cells) and a reconstituted system employing cell‐derived granules expressing either Syt‐7 or Syt‐1. First, using immunofluorescence imaging and subcellular fractionation, it is shown that Syt‐7 is widely distributed in organelles, including dense core granules. Total internal reflection fluorescence (TIRF) imaging demonstrates that the kinetics and probability of granule fusion in Syt‐7 KO cells stimulated by a native secretagogue, acetylcholine, are markedly lower than in WT cells. When fusion is observed, fluorescent cargo proteins are discharged more rapidly when only Syt‐1 is available to facilitate release. To determine the extent to which the aforementioned results are attributable purely to Syt‐7, granules expressing only Syt‐7 or Syt‐1 were triggered to fuse on planar supported bilayers bearing plasma membrane SNARE proteins. Here, as in cells, Syt‐7 confers substantially greater calcium sensitivity to granule fusion than Syt‐1 and slows the rate at which cargos are released. Overall, this study demonstrates that by virtue of its high affinity for calcium and effects on fusion pore expansion, Syt‐7 plays a central role in regulating secretory output from adrenal chromaffin cells.

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Section: Introductionmentioning

confidence: 99%

Synaptotagmin‐7 enhances calcium‐sensing of chromaffin cell granules and slows discharge of granule cargos

Bendahmane

Morales

Kreutzberger

et al. 2020

Journal of Neurochemistry

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“…Thus, basal current is more likely attributable to other sources such as noncanonical (e.g., GPCR-dependent), slow postsynaptic currents. Splanchnic neurons are also known to house and secrete a multitude of peptide cargos (12). We cannot yet account for the various ways, subtle or otherwise, in which peptidergic neurotransmission contributes to the phenomena measured here.…”

Section: Discussionmentioning

confidence: 91%

“…High frequency trains result in facilitating EPSCs in WT but not Syt7 KO synapses. Chromaffin cells of the adrenal medulla vary dramatically in the rate at which they fire (12,38). The variation in firing rate, in turn, may reflect the changing demands placed on them as effectors of the sympathetic stress response (39).…”

Section: R a F Tmentioning

confidence: 99%

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Synaptotagmin-7 participates in the regulation of acetylcholine release and short-term presynaptic facilitation in splanchnic nerve terminals

Caballero‐Florán

Bendahmane

Philippe

et al. 2020

Preprint

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The splanchnic-chromaffin cell synapse is the site at which stimulus-secretion coupling in the adrenal medulla is regulated. However, since the discovery that acetylcholine underlies chemical signaling at this synapse, attention has been disproportionately placed on postsynaptic chromaffin cell function. As a result, the determinants of Ca 2+ -sensing and exocytosis from splanchnic nerves remain poorly understood. This study shows, for the first time, that a ubiquitous Ca 2+ -binding protein, synaptotagmin-7 (Syt7) is expressed within the neurons that innervate the adrenal medulla. In synapses that lack Syt7, evoked excitatory postsynaptic currents (EPSCs) are smaller in amplitude and decay with more rapid kinetics than wild-type synapses stimulated in an identical manner. EPSCs in Syt7deficient adrenal slices also fail to facilitate, which is ordinarily a robust property of these synapses. These data are the first to implicate a role for Syt7 in regulating short-term synaptic plasticity in the peripheral nervous system. synaptotagmin | chromaffin cell | synapse | synaptic facilitation | epinephrine

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“…PACAP binds to the PAC1 receptor to trigger AMCC CAT release in response to stress (47,48). However, unlike hypoxia-induced CAT exocytosis, PACAP-induced CAT exocytosis does not rely on membrane depolarization (49).…”

Section: Role Of Nicotine and Opioid Exposure On Adrenomedullary Cat mentioning

confidence: 99%

Innervated adrenomedullary microphysiological system to model prenatal nicotine and opioid exposure

Soucy

Burchett

Brady

et al. 2020

Preprint

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The transition to extrauterine life results in a critical surge of catecholamines necessary for increased cardiovascular, respiratory, and metabolic activity. The mechanisms mediating adrenomedullary catecholamine release are poorly understood, given the sympathetic adrenomedullary control systems' functional immaturity. Important mechanistic insight is provided by newborns delivered by cesarean section or subjected to prenatal nicotine or opioid exposure, demonstrating the impaired release of adrenomedullary catecholamines. To investigate mechanisms regulating adrenomedullary innervation, we developed compartmentalized 3D microphysiological systems (MPS) by exploiting the meniscus pinning effect via GelPins, capillary pressure barriers between cell-laden hydrogels. The MPS comprises discrete 3D cultures of adrenal chromaffin cells and preganglionic sympathetic neurons within a contiguous bioengineered microtissue. Using this model, we demonstrate that adrenal chromaffin innervation plays a critical role in hypoxia-medicated catecholamine release. Furthermore, opioids and nicotine were shown to affect adrenal chromaffin cell response to a reduced oxygen environment, but neurogenic control mechanisms remained intact. GelPin containing MPS represent an inexpensive and highly adaptable approach to study innervated organ systems and improve drug screening platforms by providing innervated microenvironments.

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Cholinergic and peptidergic neurotransmission in the adrenal medulla: A dynamic control of stimulus‐secretion coupling

Cited by 24 publications

References 139 publications

Synaptotagmin‐7 enhances calcium‐sensing of chromaffin cell granules and slows discharge of granule cargos

Synaptotagmin‐7 enhances calcium‐sensing of chromaffin cell granules and slows discharge of granule cargos

Synaptotagmin-7 participates in the regulation of acetylcholine release and short-term presynaptic facilitation in splanchnic nerve terminals

Innervated adrenomedullary microphysiological system to model prenatal nicotine and opioid exposure

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