Tarantula Toxin ProTx-I Differentiates Between Human T-type Voltage-Gated Ca²⁺ Channels Ca_v3.1 and Ca_v3.2

抄録

ProTx-I peptide, a venom toxin of the tarantula Thrixopelma pruriens, has been reported to interact with voltage-gated ion channels. ProTx-I reduced Ba²⁺ currents through recombinant human T-type voltage-gated Ca²⁺ channels, Ca_v3.1 (hCa_v3.1), with roughly 160-fold more potency than through hCa_v3.2 channels. Chimeric channel proteins (hCa_v3.1/S3S4 and hCa_v3.2/S3S4) were produced by exchanging fourteen amino acids in the hCa_v3.1 domain IV S3-S4 linker region and the corresponding region of hCa_v3.2 between each other. The ProTx-I sensitivity was markedly reduced in the hCa_v3.1/S3S4 chimera as compared to the original hCa_v3.1 channel, while the hCa_v3.2/S3S4 chimera exhibited greater ProTx-I sensitivity than the original hCa_v3.2 channel. These results suggest that the domain IV S3-S4 linker in the hCa_v3.1 channel may contain residues involved in the interaction of ProTx-I with T-type Ca²⁺ channels.