Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats

Abstract It is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activati...

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Autores principales:	Xing Wang, Xuan Sun, Hou-Cheng Zhou, Fei Luo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ca63b6736ed4ae498e6d3de95c30684
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spelling	oai:doaj.org-article:4ca63b6736ed4ae498e6d3de95c306842021-12-02T18:02:23ZActivation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats10.1038/s41598-021-97769-42045-2322https://doaj.org/article/4ca63b6736ed4ae498e6d3de95c306842021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97769-4https://doaj.org/toc/2045-2322Abstract It is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activation of β3-AR exerts beneficial effects on cognitive function, the underlying cellular and molecular mechanisms have not been fully determined. In this study, whole cell patch-clamp recordings were employed to investigate the glutamatergic transmission of layer V/VI pyramidal cells in slices of the rat PFC. Our result demonstrated that SR58611A increased AMPA receptor-mediated excitatory postsynaptic currents (AMPAR-EPSCs) through activating pre-synaptic β3-AR. SR58611A enhanced the miniature EPSCs (mEPSCs) and reduced paired-pulse ratio (PPR) of AMPAR-EPSCs suggesting that SR58611A augments pre-synaptic glutamate release. SR58611A increased the number of readily releasable vesicle (N) and release probability (Pr) with no effects on the rate of recovery from vesicle depletion. Influx of Ca2+ through L-type Ca2+ channel contributed to SR58611A-mediated enhancement of glutamatergic transmission. We also found that calmodulin, myosin light chain kinase (MLCK) and myosin II were involved in SR58611A-mediated augmentation of glutamate release. Our current data suggest that SR58611A enhances glutamate release by the Ca2+/calmodulin/MLCK/myosin II pathway.Xing WangXuan SunHou-Cheng ZhouFei LuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xing Wang Xuan Sun Hou-Cheng Zhou Fei Luo Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats
description	Abstract It is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activation of β3-AR exerts beneficial effects on cognitive function, the underlying cellular and molecular mechanisms have not been fully determined. In this study, whole cell patch-clamp recordings were employed to investigate the glutamatergic transmission of layer V/VI pyramidal cells in slices of the rat PFC. Our result demonstrated that SR58611A increased AMPA receptor-mediated excitatory postsynaptic currents (AMPAR-EPSCs) through activating pre-synaptic β3-AR. SR58611A enhanced the miniature EPSCs (mEPSCs) and reduced paired-pulse ratio (PPR) of AMPAR-EPSCs suggesting that SR58611A augments pre-synaptic glutamate release. SR58611A increased the number of readily releasable vesicle (N) and release probability (Pr) with no effects on the rate of recovery from vesicle depletion. Influx of Ca2+ through L-type Ca2+ channel contributed to SR58611A-mediated enhancement of glutamatergic transmission. We also found that calmodulin, myosin light chain kinase (MLCK) and myosin II were involved in SR58611A-mediated augmentation of glutamate release. Our current data suggest that SR58611A enhances glutamate release by the Ca2+/calmodulin/MLCK/myosin II pathway.
format	article
author	Xing Wang Xuan Sun Hou-Cheng Zhou Fei Luo
author_facet	Xing Wang Xuan Sun Hou-Cheng Zhou Fei Luo
author_sort	Xing Wang
title	Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats
title_short	Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats
title_full	Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats
title_fullStr	Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats
title_full_unstemmed	Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats
title_sort	activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating ca2+/calmodulin/mlck/myosin ii pathway in the prefrontal cortex of juvenile rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4ca63b6736ed4ae498e6d3de95c30684
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Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats

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