The 27-amino acid (aa)-long d-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail , slows voltage-gated sodium (Na) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was inactive on mammalian Na1.2 and Na1.7 even at high concentrations (10 µM). Given the fact that invertebrate Na channel and T-type calcium channels (Ca3.x) are evolutionarily related, we examined the possibility that TxVIA may act on Ca3.x. Electrophysiological characterisation of the native TxVIA on Ca3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits Ca3.2 current (IC = 0.24 mM) and enhances Ca3.1 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 Na1.7 and Ca3.1 revealed that their channel binding sites contained a common epitope.
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