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 Conus textile, slows voltage-gated sodium (Na_V) 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_V1.2 and Na_V1.7 even at high concentrations (10 µM). Given the fact that invertebrate NaV channel and T-type calcium channels (Ca_V3.x) are volutionarily related, we examined the possibility that TxVIA may act on Ca_V3.x. Electrophysiological characterisation of the native TxVIA on Ca_V3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits Ca_V3.2 current (IC₅₀ = 0.24 µM) and enhances Ca_V3.1 current at higher concentrations. In fish bioassays, TxVIA showed little effect on zebrafish behaviours when injected intramuscularly at 250 ng/100 mg fish. The binding sites for TxVIA at Na_V1.7 and Ca_V3.1 revealed that their channel binding sites contained a common epitope.