Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons
Transient Receptor Potential (TRP) ion channels like Vanilloid 1 (TRPV1) and Melastatin 3 (TRPM3) are nonselective cation channels expressed in primary sensory neurons and peripheral nerve endings, which are located in cholesterol- and sphingolipid-rich membrane lipid raft regions and have important...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1452306/full |
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| author | Maja Payrits Maja Payrits Maja Payrits Balázs Zoltán Zsidó Balázs Zoltán Zsidó Andrea Kinga Nehr-Majoros Andrea Kinga Nehr-Majoros Andrea Kinga Nehr-Majoros Rita Börzsei Rita Börzsei Zsuzsanna Helyes Zsuzsanna Helyes Zsuzsanna Helyes Csaba Hetényi Csaba Hetényi Éva Szőke Éva Szőke Éva Szőke |
| author_facet | Maja Payrits Maja Payrits Maja Payrits Balázs Zoltán Zsidó Balázs Zoltán Zsidó Andrea Kinga Nehr-Majoros Andrea Kinga Nehr-Majoros Andrea Kinga Nehr-Majoros Rita Börzsei Rita Börzsei Zsuzsanna Helyes Zsuzsanna Helyes Zsuzsanna Helyes Csaba Hetényi Csaba Hetényi Éva Szőke Éva Szőke Éva Szőke |
| author_sort | Maja Payrits |
| collection | DOAJ |
| description | Transient Receptor Potential (TRP) ion channels like Vanilloid 1 (TRPV1) and Melastatin 3 (TRPM3) are nonselective cation channels expressed in primary sensory neurons and peripheral nerve endings, which are located in cholesterol- and sphingolipid-rich membrane lipid raft regions and have important roles in pain processing. Besides TRP ion channels a wide variety of voltage-gated ion channels were also described in the membrane raft regions of neuronal cells. Here we investigated the effects of lipid raft disruption by methyl-beta-cyclodextrin (MCD) and sphingomyelinase (SMase) on TRPV1, TRPM3 and voltage-gated L-type Ca2+ channel activation in cultured trigeminal neurons and sensory nerve terminals of the trachea. We also examined the mechanism of action of MCD by in silico modeling. Disruption of lipid rafts by MCD or SMase did not alter CIM0216-induced TRPM3 cation channel activation and the voltage-gated L-type Ca2+ channel activation by FPL 64126 or veratridine neither on trigeminal sensory neurons nor sensory nerve terminals. We provided the first structural explanation with in silico modeling that the activation of TRPV1, TRPM3 and voltage-gated L-type Ca2+ channels is affected differently by the cholesterol content surrounding them in the plasma membrane. It is concluded that modifying the hydrophobic interactions between lipid rafts and ion channels might provide a selective novel mechanism for peripheral analgesia. |
| format | Article |
| id | doaj-art-e9f2aa3183e84344a3e132c11e562e75 |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-e9f2aa3183e84344a3e132c11e562e752025-08-20T02:07:02ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-11-011210.3389/fcell.2024.14523061452306Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neuronsMaja Payrits0Maja Payrits1Maja Payrits2Balázs Zoltán Zsidó3Balázs Zoltán Zsidó4Andrea Kinga Nehr-Majoros5Andrea Kinga Nehr-Majoros6Andrea Kinga Nehr-Majoros7Rita Börzsei8Rita Börzsei9Zsuzsanna Helyes10Zsuzsanna Helyes11Zsuzsanna Helyes12Csaba Hetényi13Csaba Hetényi14Éva Szőke15Éva Szőke16Éva Szőke17Department of Pharmacology and Pharmacotherapy, Medical School and Centre for Neuroscience, University of Pécs, Pécs, HungaryNational Laboratory for Drug Research and Development, Budapest, HungaryHungarian Research Network, Chronic Pain Research Group, Pécs, HungaryNational Laboratory for Drug Research and Development, Budapest, HungaryPharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School and Centre for Neuroscience, University of Pécs, Pécs, HungaryNational Laboratory for Drug Research and Development, Budapest, HungaryHungarian Research Network, Chronic Pain Research Group, Pécs, HungaryNational Laboratory for Drug Research and Development, Budapest, HungaryPharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School and Centre for Neuroscience, University of Pécs, Pécs, HungaryNational Laboratory for Drug Research and Development, Budapest, HungaryHungarian Research Network, Chronic Pain Research Group, Pécs, HungaryNational Laboratory for Drug Research and Development, Budapest, HungaryPharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School and Centre for Neuroscience, University of Pécs, Pécs, HungaryNational Laboratory for Drug Research and Development, Budapest, HungaryHungarian Research Network, Chronic Pain Research Group, Pécs, HungaryTransient Receptor Potential (TRP) ion channels like Vanilloid 1 (TRPV1) and Melastatin 3 (TRPM3) are nonselective cation channels expressed in primary sensory neurons and peripheral nerve endings, which are located in cholesterol- and sphingolipid-rich membrane lipid raft regions and have important roles in pain processing. Besides TRP ion channels a wide variety of voltage-gated ion channels were also described in the membrane raft regions of neuronal cells. Here we investigated the effects of lipid raft disruption by methyl-beta-cyclodextrin (MCD) and sphingomyelinase (SMase) on TRPV1, TRPM3 and voltage-gated L-type Ca2+ channel activation in cultured trigeminal neurons and sensory nerve terminals of the trachea. We also examined the mechanism of action of MCD by in silico modeling. Disruption of lipid rafts by MCD or SMase did not alter CIM0216-induced TRPM3 cation channel activation and the voltage-gated L-type Ca2+ channel activation by FPL 64126 or veratridine neither on trigeminal sensory neurons nor sensory nerve terminals. We provided the first structural explanation with in silico modeling that the activation of TRPV1, TRPM3 and voltage-gated L-type Ca2+ channels is affected differently by the cholesterol content surrounding them in the plasma membrane. It is concluded that modifying the hydrophobic interactions between lipid rafts and ion channels might provide a selective novel mechanism for peripheral analgesia.https://www.frontiersin.org/articles/10.3389/fcell.2024.1452306/fullTRPV1TRPM3L-type voltage-gated Ca2+ channelCIM0216FPL 64176veratridine |
| spellingShingle | Maja Payrits Maja Payrits Maja Payrits Balázs Zoltán Zsidó Balázs Zoltán Zsidó Andrea Kinga Nehr-Majoros Andrea Kinga Nehr-Majoros Andrea Kinga Nehr-Majoros Rita Börzsei Rita Börzsei Zsuzsanna Helyes Zsuzsanna Helyes Zsuzsanna Helyes Csaba Hetényi Csaba Hetényi Éva Szőke Éva Szőke Éva Szőke Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons Frontiers in Cell and Developmental Biology TRPV1 TRPM3 L-type voltage-gated Ca2+ channel CIM0216 FPL 64176 veratridine |
| title | Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons |
| title_full | Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons |
| title_fullStr | Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons |
| title_full_unstemmed | Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons |
| title_short | Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons |
| title_sort | lipid raft disruption inhibits the activation of transient receptor potential vanilloid 1 but not trp melastatin 3 and the voltage gated l type calcium channels in sensory neurons |
| topic | TRPV1 TRPM3 L-type voltage-gated Ca2+ channel CIM0216 FPL 64176 veratridine |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1452306/full |
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