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Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration

Glucocorticoids rapidly stimulate endocannabinoid synthesis and modulation of synaptic transmission in hypothalamic neuroendocrine cells via a nongenomic signaling mechanism. The endocannabinoid actions are synapse-constrained by astrocyte restriction of extracellular spatial domains. Exogenous cann...

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Autores principales: Wu, Ning, Tasker, Jeffrey G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617081/
https://www.ncbi.nlm.nih.gov/pubmed/28966975
http://dx.doi.org/10.1523/ENEURO.0216-17.2017
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author Wu, Ning
Tasker, Jeffrey G.
author_facet Wu, Ning
Tasker, Jeffrey G.
author_sort Wu, Ning
collection PubMed
description Glucocorticoids rapidly stimulate endocannabinoid synthesis and modulation of synaptic transmission in hypothalamic neuroendocrine cells via a nongenomic signaling mechanism. The endocannabinoid actions are synapse-constrained by astrocyte restriction of extracellular spatial domains. Exogenous cannabinoids have been shown to modulate postsynaptic potassium currents, including the A-type potassium current (I(A)), in different cell types. The activity of magnocellular neuroendocrine cells is shaped by a prominent I(A). We tested for a rapid glucocorticoid modulation of the postsynaptic I(K) and I(A) in magnocellular neuroendocrine cells of the hypothalamic paraventricular nucleus (PVN) using whole-cell recordings in rat brain slices. Application of the synthetic glucocorticoid dexamethasone (Dex) had no rapid effect on the I(K) or I(A) amplitude, voltage dependence, or kinetics in magnocellular neurons in slices from untreated rats. In magnocellular neurons from salt-loaded rats, however, Dex application caused a rapid suppression of the I(A) and a depolarizing shift in I(A) voltage dependence. Exogenously applied endocannabinoids mimicked the rapid Dex modulation of the I(A), and CB1 receptor antagonists and agonists blocked and occluded the Dex-induced changes in the I(A), respectively, suggesting an endocannabinoid dependence of the rapid glucocorticoid effect. Preincubation of control slices in a gliotoxin resulted in the partial recapitulation of the glucocorticoid-induced rapid suppression of the I(A). These findings demonstrate a glucocorticoid suppression of the postsynaptic I(A) in PVN magnocellular neurons via an autocrine endocannabinoid-dependent mechanism following chronic dehydration, and suggest a possible role for astrocytes in the control of the autocrine endocannabinoid actions.
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spelling pubmed-56170812017-09-29 Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration Wu, Ning Tasker, Jeffrey G. eNeuro New Research Glucocorticoids rapidly stimulate endocannabinoid synthesis and modulation of synaptic transmission in hypothalamic neuroendocrine cells via a nongenomic signaling mechanism. The endocannabinoid actions are synapse-constrained by astrocyte restriction of extracellular spatial domains. Exogenous cannabinoids have been shown to modulate postsynaptic potassium currents, including the A-type potassium current (I(A)), in different cell types. The activity of magnocellular neuroendocrine cells is shaped by a prominent I(A). We tested for a rapid glucocorticoid modulation of the postsynaptic I(K) and I(A) in magnocellular neuroendocrine cells of the hypothalamic paraventricular nucleus (PVN) using whole-cell recordings in rat brain slices. Application of the synthetic glucocorticoid dexamethasone (Dex) had no rapid effect on the I(K) or I(A) amplitude, voltage dependence, or kinetics in magnocellular neurons in slices from untreated rats. In magnocellular neurons from salt-loaded rats, however, Dex application caused a rapid suppression of the I(A) and a depolarizing shift in I(A) voltage dependence. Exogenously applied endocannabinoids mimicked the rapid Dex modulation of the I(A), and CB1 receptor antagonists and agonists blocked and occluded the Dex-induced changes in the I(A), respectively, suggesting an endocannabinoid dependence of the rapid glucocorticoid effect. Preincubation of control slices in a gliotoxin resulted in the partial recapitulation of the glucocorticoid-induced rapid suppression of the I(A). These findings demonstrate a glucocorticoid suppression of the postsynaptic I(A) in PVN magnocellular neurons via an autocrine endocannabinoid-dependent mechanism following chronic dehydration, and suggest a possible role for astrocytes in the control of the autocrine endocannabinoid actions. Society for Neuroscience 2017-09-19 /pmc/articles/PMC5617081/ /pubmed/28966975 http://dx.doi.org/10.1523/ENEURO.0216-17.2017 Text en Copyright © 2017 Wu and Tasker http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Wu, Ning
Tasker, Jeffrey G.
Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration
title Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration
title_full Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration
title_fullStr Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration
title_full_unstemmed Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration
title_short Nongenomic Glucocorticoid Suppression of a Postsynaptic Potassium Current via Emergent Autocrine Endocannabinoid Signaling in Hypothalamic Neuroendocrine Cells following Chronic Dehydration
title_sort nongenomic glucocorticoid suppression of a postsynaptic potassium current via emergent autocrine endocannabinoid signaling in hypothalamic neuroendocrine cells following chronic dehydration
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617081/
https://www.ncbi.nlm.nih.gov/pubmed/28966975
http://dx.doi.org/10.1523/ENEURO.0216-17.2017
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