PUBLICATION
Characterisation of d-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator
- Authors
- Wang, D., Himaya, S.W.A., Giacomotto, J., Hasan, M.M., Cardoso, F.C., Ragnarsson, L., Lewis, R.J.
- ID
- ZDB-PUB-200708-17
- Date
- 2020
- Source
- Marine drugs 18(7): (Journal)
- Registered Authors
- Giacomotto, Jean
- Keywords
- TxVIA, mammalian NaV channel, selective inhibitor, T-type CaV3.2
- MeSH Terms
-
- Animals
- Calcium Channels, T-Type
- Cell Line
- Conotoxins/pharmacology*
- Humans
- Models, Molecular
- Protein Binding
- Protein Conformation
- Rats
- Zebrafish
- PubMed
- 32629781 Full text @ Mar. Drugs
Citation
Wang, D., Himaya, S.W.A., Giacomotto, J., Hasan, M.M., Cardoso, F.C., Ragnarsson, L., Lewis, R.J. (2020) Characterisation of d-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator. Marine drugs. 18(7).
Abstract
The 27-amino acid (aa)-long d-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail Conus textile, slows voltage-gated sodium (NaV) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was inactive on mammalian NaV1.2 and NaV1.7 even at high concentrations (10 µM). Given the fact that invertebrate NaV channel and T-type calcium channels (CaV3.x) are evolutionarily related, we examined the possibility that TxVIA may act on CaV3.x. Electrophysiological characterisation of the native TxVIA on CaV3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits CaV3.2 current (IC50 = 0.24 mM) and enhances CaV3.1 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 NaV1.7 and CaV3.1 revealed that their channel binding sites contained a common epitope.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping