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Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission

In cholinergic synapses, the neurotransmitter acetylcholine (ACh) is rapidly hydrolyzed by esterases to choline and acetic acid (AH). It is believed that this reaction serves the purpose of deactivating ACh once it has exerted its effect on a receptor protein (AChR). The protons liberated in this re...

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Autores principales: Fillafer, Christian, Koll, Yana S., Schneider, Matthias F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781637/
https://www.ncbi.nlm.nih.gov/pubmed/35054529
http://dx.doi.org/10.3390/membranes12010005
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author Fillafer, Christian
Koll, Yana S.
Schneider, Matthias F.
author_facet Fillafer, Christian
Koll, Yana S.
Schneider, Matthias F.
author_sort Fillafer, Christian
collection PubMed
description In cholinergic synapses, the neurotransmitter acetylcholine (ACh) is rapidly hydrolyzed by esterases to choline and acetic acid (AH). It is believed that this reaction serves the purpose of deactivating ACh once it has exerted its effect on a receptor protein (AChR). The protons liberated in this reaction, however, may by themselves excite the postsynaptic membrane. Herein, we investigated the response of cell membrane models made from phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) to ACh in the presence and absence of acetylcholinesterase (AChE). Without a catalyst, there were no significant effects of ACh on the membrane state (lateral pressure change [Formula: see text] mN/m). In contrast, strong responses were observed in membranes made from PS and PA when ACh was applied in presence of AChE (>5 mN/m). Control experiments demonstrated that this effect was due to the protonation of lipid headgroups, which is maximal at the pK (for PS: [Formula: see text]; for PA: [Formula: see text]). These findings are physiologically relevant, because both of these lipids are present in postsynaptic membranes. Furthermore, we discussed evidence which suggests that AChR assembles a lipid-protein interface that is proton-sensitive in the vicinity of pH [Formula: see text]. Such a membrane could be excited by hydrolysis of micromolar amounts of ACh. Based on these results, we proposed that cholinergic transmission is due to postsynaptic membrane protonation. Our model will be falsified if cholinergic membranes do not respond to acidification.
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spelling pubmed-87816372022-01-22 Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission Fillafer, Christian Koll, Yana S. Schneider, Matthias F. Membranes (Basel) Article In cholinergic synapses, the neurotransmitter acetylcholine (ACh) is rapidly hydrolyzed by esterases to choline and acetic acid (AH). It is believed that this reaction serves the purpose of deactivating ACh once it has exerted its effect on a receptor protein (AChR). The protons liberated in this reaction, however, may by themselves excite the postsynaptic membrane. Herein, we investigated the response of cell membrane models made from phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) to ACh in the presence and absence of acetylcholinesterase (AChE). Without a catalyst, there were no significant effects of ACh on the membrane state (lateral pressure change [Formula: see text] mN/m). In contrast, strong responses were observed in membranes made from PS and PA when ACh was applied in presence of AChE (>5 mN/m). Control experiments demonstrated that this effect was due to the protonation of lipid headgroups, which is maximal at the pK (for PS: [Formula: see text]; for PA: [Formula: see text]). These findings are physiologically relevant, because both of these lipids are present in postsynaptic membranes. Furthermore, we discussed evidence which suggests that AChR assembles a lipid-protein interface that is proton-sensitive in the vicinity of pH [Formula: see text]. Such a membrane could be excited by hydrolysis of micromolar amounts of ACh. Based on these results, we proposed that cholinergic transmission is due to postsynaptic membrane protonation. Our model will be falsified if cholinergic membranes do not respond to acidification. MDPI 2021-12-21 /pmc/articles/PMC8781637/ /pubmed/35054529 http://dx.doi.org/10.3390/membranes12010005 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fillafer, Christian
Koll, Yana S.
Schneider, Matthias F.
Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission
title Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission
title_full Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission
title_fullStr Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission
title_full_unstemmed Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission
title_short Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission
title_sort lipid membrane state change by catalytic protonation and the implications for synaptic transmission
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781637/
https://www.ncbi.nlm.nih.gov/pubmed/35054529
http://dx.doi.org/10.3390/membranes12010005
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