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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MDPI AG
2021-12-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/12/1/5 |
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| author | Christian Fillafer Yana S. Koll Matthias F. Schneider |
| author_facet | Christian Fillafer Yana S. Koll Matthias F. Schneider |
| author_sort | Christian Fillafer |
| collection | DOAJ |
| 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>≤</mo><mn>0.5</mn></mrow></semantics></math></inline-formula> 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: <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>pK</mi><mrow><mi>COOH</mi></mrow></msub><mo>≈</mo><mn>5.0</mn></mrow></semantics></math></inline-formula>; for PA: <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>pK</mi><mrow><msubsup><mi>HPO</mi><mrow><mn>4</mn></mrow><mo>−</mo></msubsup></mrow></msub><mo>≈</mo><mn>8.5</mn></mrow></semantics></math></inline-formula>). 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>7.5</mn></mrow></semantics></math></inline-formula>. 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. |
| first_indexed | 2024-03-10T00:59:50Z |
| format | Article |
| id | doaj.art-9907760c403b47898ea0466b705e4106 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-10T00:59:50Z |
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| spelling | doaj.art-9907760c403b47898ea0466b705e41062023-11-23T14:37:47ZengMDPI AGMembranes2077-03752021-12-01121510.3390/membranes12010005Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic TransmissionChristian Fillafer0Yana S. Koll1Matthias F. Schneider2Medical and Biological Physics, Department of Physics, Technical University Dortmund, Otto-Hahn-Str. 4, 44227 Dortmund, GermanyMedical and Biological Physics, Department of Physics, Technical University Dortmund, Otto-Hahn-Str. 4, 44227 Dortmund, GermanyMedical and Biological Physics, Department of Physics, Technical University Dortmund, Otto-Hahn-Str. 4, 44227 Dortmund, GermanyIn 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>≤</mo><mn>0.5</mn></mrow></semantics></math></inline-formula> 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: <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>pK</mi><mrow><mi>COOH</mi></mrow></msub><mo>≈</mo><mn>5.0</mn></mrow></semantics></math></inline-formula>; for PA: <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>pK</mi><mrow><msubsup><mi>HPO</mi><mrow><mn>4</mn></mrow><mo>−</mo></msubsup></mrow></msub><mo>≈</mo><mn>8.5</mn></mrow></semantics></math></inline-formula>). 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>7.5</mn></mrow></semantics></math></inline-formula>. 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.https://www.mdpi.com/2077-0375/12/1/5acetylcholineacetic acidprotonpHsynapseacetylcholine receptor (AChR) |
| spellingShingle | Christian Fillafer Yana S. Koll Matthias F. Schneider Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission Membranes acetylcholine acetic acid proton pH synapse acetylcholine receptor (AChR) |
| 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 | acetylcholine acetic acid proton pH synapse acetylcholine receptor (AChR) |
| url | https://www.mdpi.com/2077-0375/12/1/5 |
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