The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins
Neurotoxin receptor site 1, in the outer vestibule of the conducting pore of voltage-gated sodium channels (VGSCs), was first functionally defined by its ability to bind the guanidinium-containing agents, tetrodotoxin (TTX) and saxitoxin (STX). Subsequent studies showed that peptide μ-conotoxins com...
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| Format: | Article |
| Language: | English |
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MDPI AG
2010-07-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/8/7/2153/ |
| _version_ | 1828116470057402368 |
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| author | Baldomero M. Olivera Michael F. Sheets Robert J. French Doju Yoshikami |
| author_facet | Baldomero M. Olivera Michael F. Sheets Robert J. French Doju Yoshikami |
| author_sort | Baldomero M. Olivera |
| collection | DOAJ |
| description | Neurotoxin receptor site 1, in the outer vestibule of the conducting pore of voltage-gated sodium channels (VGSCs), was first functionally defined by its ability to bind the guanidinium-containing agents, tetrodotoxin (TTX) and saxitoxin (STX). Subsequent studies showed that peptide μ-conotoxins competed for binding at site 1. All of these natural inhibitors block single sodium channels in an all-or-none manner on binding. With the discovery of an increasing variety of μ-conotoxins, and the synthesis of numerous derivatives, observed interactions between the channel and these different ligands have become more complex. Certain μ-conotoxin derivatives block single-channel currents partially, rather than completely, thus enabling the demonstration of interactions between the bound toxin and the channel’s voltage sensor. Most recently, the relatively small μ-conotoxin KIIIA (16 amino acids) and its variants have been shown to bind simultaneously with TTX and exhibit both synergistic and antagonistic interactions with TTX. These interactions raise new pharmacological possibilities and place new constraints on the possible structures of the bound complexes of VGSCs with these toxins. |
| first_indexed | 2024-04-11T12:57:22Z |
| format | Article |
| id | doaj.art-8084868ebe444930acc429096e6c26f5 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T12:57:22Z |
| publishDate | 2010-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-8084868ebe444930acc429096e6c26f52022-12-22T04:23:03ZengMDPI AGMarine Drugs1660-33972010-07-01872153216110.3390/md8072153The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-ConotoxinsBaldomero M. OliveraMichael F. SheetsRobert J. FrenchDoju YoshikamiNeurotoxin receptor site 1, in the outer vestibule of the conducting pore of voltage-gated sodium channels (VGSCs), was first functionally defined by its ability to bind the guanidinium-containing agents, tetrodotoxin (TTX) and saxitoxin (STX). Subsequent studies showed that peptide μ-conotoxins competed for binding at site 1. All of these natural inhibitors block single sodium channels in an all-or-none manner on binding. With the discovery of an increasing variety of μ-conotoxins, and the synthesis of numerous derivatives, observed interactions between the channel and these different ligands have become more complex. Certain μ-conotoxin derivatives block single-channel currents partially, rather than completely, thus enabling the demonstration of interactions between the bound toxin and the channel’s voltage sensor. Most recently, the relatively small μ-conotoxin KIIIA (16 amino acids) and its variants have been shown to bind simultaneously with TTX and exhibit both synergistic and antagonistic interactions with TTX. These interactions raise new pharmacological possibilities and place new constraints on the possible structures of the bound complexes of VGSCs with these toxins.http://www.mdpi.com/1660-3397/8/7/2153/guanidinium toxinsconopeptidespore block |
| spellingShingle | Baldomero M. Olivera Michael F. Sheets Robert J. French Doju Yoshikami The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins Marine Drugs guanidinium toxins conopeptides pore block |
| title | The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins |
| title_full | The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins |
| title_fullStr | The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins |
| title_full_unstemmed | The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins |
| title_short | The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins |
| title_sort | tetrodotoxin receptor of voltage gated sodium channels perspectives from interactions with μ conotoxins |
| topic | guanidinium toxins conopeptides pore block |
| url | http://www.mdpi.com/1660-3397/8/7/2153/ |
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