Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator
The 27-amino acid (aa)-long δ-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail <i>Conus textile</i>, slows voltage-gated sodium (Na<sub>V</sub>) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In th...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/7/343 |
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| author | Dan Wang S.W.A. Himaya Jean Giacomotto Md. Mahadhi Hasan Fernanda C. Cardoso Lotten Ragnarsson Richard J. Lewis |
| author_facet | Dan Wang S.W.A. Himaya Jean Giacomotto Md. Mahadhi Hasan Fernanda C. Cardoso Lotten Ragnarsson Richard J. Lewis |
| author_sort | Dan Wang |
| collection | DOAJ |
| description | The 27-amino acid (aa)-long δ-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail <i>Conus textile</i>, slows voltage-gated sodium (Na<sub>V</sub>) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was inactive on mammalian Na<sub>V</sub>1.2 and Na<sub>V</sub>1.7 even at high concentrations (10 µM). Given the fact that invertebrate Na<sub>V</sub> channel and T-type calcium channels (Ca<sub>V</sub>3.x) are evolutionarily related, we examined the possibility that TxVIA may act on Ca<sub>V</sub>3.x. Electrophysiological characterisation of the native TxVIA on Ca<sub>V</sub>3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits Ca<sub>V</sub>3.2 current (IC<sub>50</sub> = 0.24 μM) and enhances Ca<sub>V</sub>3.1 current at higher concentrations. In fish bioassays TxVIA showed little effect on zebrafish behaviours when injected intramuscular at 250 ng/100 mg fish. The binding sites for TxVIA at Na<sub>V</sub>1.7 and Ca<sub>V</sub>3.1 revealed that their channel binding sites contained a common epitope. |
| first_indexed | 2024-03-10T18:48:14Z |
| format | Article |
| id | doaj.art-394de7d138044b069d2c922c18248773 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T18:48:14Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-394de7d138044b069d2c922c182487732023-11-20T05:21:28ZengMDPI AGMarine Drugs1660-33972020-06-0118734310.3390/md18070343Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel ModulatorDan Wang0S.W.A. Himaya1Jean Giacomotto2Md. Mahadhi Hasan3Fernanda C. Cardoso4Lotten Ragnarsson5Richard J. Lewis6Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaQueensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe 27-amino acid (aa)-long δ-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail <i>Conus textile</i>, slows voltage-gated sodium (Na<sub>V</sub>) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was inactive on mammalian Na<sub>V</sub>1.2 and Na<sub>V</sub>1.7 even at high concentrations (10 µM). Given the fact that invertebrate Na<sub>V</sub> channel and T-type calcium channels (Ca<sub>V</sub>3.x) are evolutionarily related, we examined the possibility that TxVIA may act on Ca<sub>V</sub>3.x. Electrophysiological characterisation of the native TxVIA on Ca<sub>V</sub>3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits Ca<sub>V</sub>3.2 current (IC<sub>50</sub> = 0.24 μM) and enhances Ca<sub>V</sub>3.1 current at higher concentrations. In fish bioassays TxVIA showed little effect on zebrafish behaviours when injected intramuscular at 250 ng/100 mg fish. The binding sites for TxVIA at Na<sub>V</sub>1.7 and Ca<sub>V</sub>3.1 revealed that their channel binding sites contained a common epitope.https://www.mdpi.com/1660-3397/18/7/343TxVIAmammalian Na<sub>V</sub> channelselective inhibitorT-type Ca<sub>V</sub>3.2 |
| spellingShingle | Dan Wang S.W.A. Himaya Jean Giacomotto Md. Mahadhi Hasan Fernanda C. Cardoso Lotten Ragnarsson Richard J. Lewis Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator Marine Drugs TxVIA mammalian Na<sub>V</sub> channel selective inhibitor T-type Ca<sub>V</sub>3.2 |
| title | Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator |
| title_full | Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator |
| title_fullStr | Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator |
| title_full_unstemmed | Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator |
| title_short | Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator |
| title_sort | characterisation of δ conotoxin txvia as a mammalian t type calcium channel modulator |
| topic | TxVIA mammalian Na<sub>V</sub> channel selective inhibitor T-type Ca<sub>V</sub>3.2 |
| url | https://www.mdpi.com/1660-3397/18/7/343 |
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