Kurtoxin

Kurtoxin is a toxin found in the venom of the scorpion "Parabuthus transvaalicus". It affects the gating of voltage-gated sodium channels and calcium channels.

Source

Kurtotoxin is found in the venom of the South African scorpion "Parabuthus transvaalicus".

Chemistry

Kurtoxin is a protein containing 63 amino acid residues with a mass of 7386.1 daltons. It can be isolated from the venom of "Parabuthus transvaalicus" by reversed-phase high-performance liquid chromatography (HPLC). Kurtoxin is closely related to α-scorpion toxins, a family of toxins that slow inactivation of voltage-gated sodium channels. The complete primary amino-acid sequence of kurtoxin is: KIDGYPVDYW NCKRICWYNN KYCNDLCKGL KADSGYCWGW TLSCYCQGLP DNARIKRSGR CRA.

Target

In research on Xenopus oocytes it was found that kurtoxin affects low-threshold α1G and α1H calcium channels, but not the high-threshold α1A, α1B, α1C, and α1E Ca channels. Like other α-scorpion toxins kurtoxin was also found to interact with voltage-gated sodium channels. In rat neurons, less selectivity for kurtoxin on calcium channels is found. Here the toxin interacts with high affinity with T-type, L-type, N-type, and P-type channels.

Mode of action

Kurtoxin inhibits ion calcium channels by modifying channel gating. The effect of the toxin is voltage-dependent. In a voltage-clamp experiment it was found that calcium channels are more strongly inhibited by minor depolarization than by a strong depolarization of the cell. The peptide toxin binds close to the channel voltage sensor and thereby produces complex gating modifications specific for each channel type. In rats, kurtoxin inhibited T-type, L-type, and N-type Ca channels and facilitated P-type channels. Deactivation was accelerated in T-type and L-type channels, slowed down in P-type channels and not affected in N-type calcium channels. Kurtoxin also has an effect on sodium channels. It slows down both activation and inactivation of the channel.

References

Chuang, R.S., Jaffe, H., Cribbs, L., Perez-Reyes, E., Schwartz, K.J. (1998). Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nature Neuroscience 1(8), 668-674. [http://www.jneurosci.org/cgi/reprint/22/6/2023]

Sidach, S.S., Mintz, I.M. (2002). Kurtoxin, a gating modifier of neuronal high- and low threshold Ca channels. The Journal of Neuroscience, 22(6), 2023-2034. [http://jpet.aspetjournals.org/cgi/reprint/314/3/1370]