Tarantula toxin ProTx-I differentiates between human T-type voltage-gated Ca2+ Channels Cav3.1 and Cav3.2

ProTx-I peptide, a venom toxin of the tarantula Thrixopelma pruriens, has been reported to interact with voltage-gated ion channels. ProTx-I reduced Ba(2+) currents through recombinant human T-type voltage-gated Ca(2+) channels, Ca(v)3.1 (hCa(v)3.1), with roughly 160-fold more potency than through hCa(v)3.2 channels. Chimeric channel proteins (hCa(v)3.1/S3S4 and hCa(v)3.2/S3S4) were produced by exchanging fourteen Amino acids in the hCa(v)3.1 domain IV S3-S4 linker region and the corresponding region of hCa(v)3.2 between each other. The ProTx-I sensitivity was markedly reduced in the hCa(v)3.1/S3S4 chimera as compared to the original hCa(v)3.1 channel, while the hCa(v)3.2/S3S4 chimera exhibited greater ProTx-I sensitivity than the original hCa(v)3.2 channel. These results suggest that the domain IV S3-S4 linker in the hCa(v)3.1 channel may contain residues involved in the interaction of ProTx-I with T-type Ca(2+) channels.