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Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator

1
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
2
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
3
Queensland Centre for Mental Health Research, West Moreton Hospital and Health Service and University of Queensland, Brisbane, QLD 4072, Australia
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(7), 343; https://doi.org/10.3390/md18070343
Received: 12 May 2020 / Revised: 25 June 2020 / Accepted: 25 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
The 27-amino acid (aa)-long δ-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 μM) 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. View Full-Text
Keywords: TxVIA; mammalian NaV channel; selective inhibitor; T-type CaV3.2 TxVIA; mammalian NaV channel; selective inhibitor; T-type CaV3.2
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Wang, D.; Himaya, S.; Giacomotto, J.; Hasan, M.M.; Cardoso, F.C.; Ragnarsson, L.; Lewis, R.J. Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator. Mar. Drugs 2020, 18, 343.

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