Ammonium chloride alters neuronal excitability and synaptic vesicle release

Abstract Genetically encoded pH-sensors are widely used in studying cell membrane trafficking and membrane protein turnover because they render exo-/endocytosis-associated pH changes to fluorescent signals. For imaging and analysis purposes, high concentration ammonium chloride is routinely used to...

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Autores principales:	Roman M. Lazarenko, Claire E. DelBove, Claire E. Strothman, Qi Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c15e862805f8466da2a556b869711f93
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spelling	oai:doaj.org-article:c15e862805f8466da2a556b869711f932021-12-02T11:52:19ZAmmonium chloride alters neuronal excitability and synaptic vesicle release10.1038/s41598-017-05338-52045-2322https://doaj.org/article/c15e862805f8466da2a556b869711f932017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05338-5https://doaj.org/toc/2045-2322Abstract Genetically encoded pH-sensors are widely used in studying cell membrane trafficking and membrane protein turnover because they render exo-/endocytosis-associated pH changes to fluorescent signals. For imaging and analysis purposes, high concentration ammonium chloride is routinely used to alkalize intracellular membrane compartments under the assumption that it does not cause long-term effects on cellular processes being studied like neurotransmission. However, pathological studies about hyperammonemia have shown that ammonium is toxic to brain cells especially astrocytes and neurons. Here, we focus on ammonium’s physiological impacts on neurons including membrane potential, cytosolic Ca2+ and synaptic vesicles. We have found that extracellularly applied ammonium chloride as low as 5 mM causes intracellular Ca2+-increase and a reduction of vesicle release even after washout. The often-used 50 mM ammonium chloride causes more extensive and persistent changes, including membrane depolarization, prolonged elevation of intracellular Ca2+ and diminution of releasable synaptic vesicles. Our findings not only help to bridge the discrepancies in previous studies about synaptic vesicle release using those pH-sensors or other vesicle specific reporters, but also suggest an intriguing relationship between intracellular pH and neurotransmission.Roman M. LazarenkoClaire E. DelBoveClaire E. StrothmanQi ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Roman M. Lazarenko Claire E. DelBove Claire E. Strothman Qi Zhang Ammonium chloride alters neuronal excitability and synaptic vesicle release
description	Abstract Genetically encoded pH-sensors are widely used in studying cell membrane trafficking and membrane protein turnover because they render exo-/endocytosis-associated pH changes to fluorescent signals. For imaging and analysis purposes, high concentration ammonium chloride is routinely used to alkalize intracellular membrane compartments under the assumption that it does not cause long-term effects on cellular processes being studied like neurotransmission. However, pathological studies about hyperammonemia have shown that ammonium is toxic to brain cells especially astrocytes and neurons. Here, we focus on ammonium’s physiological impacts on neurons including membrane potential, cytosolic Ca2+ and synaptic vesicles. We have found that extracellularly applied ammonium chloride as low as 5 mM causes intracellular Ca2+-increase and a reduction of vesicle release even after washout. The often-used 50 mM ammonium chloride causes more extensive and persistent changes, including membrane depolarization, prolonged elevation of intracellular Ca2+ and diminution of releasable synaptic vesicles. Our findings not only help to bridge the discrepancies in previous studies about synaptic vesicle release using those pH-sensors or other vesicle specific reporters, but also suggest an intriguing relationship between intracellular pH and neurotransmission.
format	article
author	Roman M. Lazarenko Claire E. DelBove Claire E. Strothman Qi Zhang
author_facet	Roman M. Lazarenko Claire E. DelBove Claire E. Strothman Qi Zhang
author_sort	Roman M. Lazarenko
title	Ammonium chloride alters neuronal excitability and synaptic vesicle release
title_short	Ammonium chloride alters neuronal excitability and synaptic vesicle release
title_full	Ammonium chloride alters neuronal excitability and synaptic vesicle release
title_fullStr	Ammonium chloride alters neuronal excitability and synaptic vesicle release
title_full_unstemmed	Ammonium chloride alters neuronal excitability and synaptic vesicle release
title_sort	ammonium chloride alters neuronal excitability and synaptic vesicle release
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c15e862805f8466da2a556b869711f93
work_keys_str_mv	AT romanmlazarenko ammoniumchloridealtersneuronalexcitabilityandsynapticvesiclerelease AT claireedelbove ammoniumchloridealtersneuronalexcitabilityandsynapticvesiclerelease AT claireestrothman ammoniumchloridealtersneuronalexcitabilityandsynapticvesiclerelease AT qizhang ammoniumchloridealtersneuronalexcitabilityandsynapticvesiclerelease
_version_	1718395129752977408

Ammonium chloride alters neuronal excitability and synaptic vesicle release

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