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Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes
Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecul...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703819/ https://www.ncbi.nlm.nih.gov/pubmed/34947764 http://dx.doi.org/10.3390/nano11123410 |
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author | Al Kury, Lina T. Papandreou, Dimitrios Hurmach, Vasyl V. Dryn, Dariia O. Melnyk, Mariia I. Platonov, Maxim O. Prylutskyy, Yuriy I. Ritter, Uwe Scharff, Peter Zholos, Alexander V. |
author_facet | Al Kury, Lina T. Papandreou, Dimitrios Hurmach, Vasyl V. Dryn, Dariia O. Melnyk, Mariia I. Platonov, Maxim O. Prylutskyy, Yuriy I. Ritter, Uwe Scharff, Peter Zholos, Alexander V. |
author_sort | Al Kury, Lina T. |
collection | PubMed |
description | Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mI(CAT)), induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration. Here, we use molecular docking/molecular dynamics simulations and direct patch-clamp recordings of whole-cell currents to show that SWCNTs, purified and functionalized by carboxylation in water suspension containing single SWCNTs with a diameter of 0.5–1.5 nm, can inhibit mI(CAT), which is mainly carried by TRPC4 cation channels in ileal smooth muscle cells, and is the main regulator of cholinergic excitation–contraction coupling in the small intestinal tract. This inhibition was voltage-independent and associated with a shortening of the mean open time of the channel. These results suggest that SWCNTs cause a direct blockage of the TRPC4 channel and may represent a novel class of TRPC4 modulators. |
format | Online Article Text |
id | pubmed-8703819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87038192021-12-25 Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes Al Kury, Lina T. Papandreou, Dimitrios Hurmach, Vasyl V. Dryn, Dariia O. Melnyk, Mariia I. Platonov, Maxim O. Prylutskyy, Yuriy I. Ritter, Uwe Scharff, Peter Zholos, Alexander V. Nanomaterials (Basel) Article Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mI(CAT)), induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration. Here, we use molecular docking/molecular dynamics simulations and direct patch-clamp recordings of whole-cell currents to show that SWCNTs, purified and functionalized by carboxylation in water suspension containing single SWCNTs with a diameter of 0.5–1.5 nm, can inhibit mI(CAT), which is mainly carried by TRPC4 cation channels in ileal smooth muscle cells, and is the main regulator of cholinergic excitation–contraction coupling in the small intestinal tract. This inhibition was voltage-independent and associated with a shortening of the mean open time of the channel. These results suggest that SWCNTs cause a direct blockage of the TRPC4 channel and may represent a novel class of TRPC4 modulators. MDPI 2021-12-16 /pmc/articles/PMC8703819/ /pubmed/34947764 http://dx.doi.org/10.3390/nano11123410 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 Al Kury, Lina T. Papandreou, Dimitrios Hurmach, Vasyl V. Dryn, Dariia O. Melnyk, Mariia I. Platonov, Maxim O. Prylutskyy, Yuriy I. Ritter, Uwe Scharff, Peter Zholos, Alexander V. Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes |
title | Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes |
title_full | Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes |
title_fullStr | Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes |
title_full_unstemmed | Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes |
title_short | Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes |
title_sort | single-walled carbon nanotubes inhibit trpc4-mediated muscarinic cation current in mouse ileal myocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703819/ https://www.ncbi.nlm.nih.gov/pubmed/34947764 http://dx.doi.org/10.3390/nano11123410 |
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