Colombian Scorpion Centruroides margaritatus: Purification and Characterization of a Gamma Potassium Toxin with Full-Block Activity on the hERG1 Channel

The Colombian scorpion Centruroides margaritatus produces a venom considered of low toxicity. Nevertheless, there are known cases of envenomation resulting in cardiovascular disorders, probably due to venom components that target ion channels. Among them, the human ether-a-go-go-Related gene (hERG1) potassium channels are critical for cardiac action potential repolarization and alteration in its functionality are associated with cardiac disorders. This work describes the purification and electrophysiological characterization of a Centruroides margaritatus venom component acting on hERG1 channels, the CmERG1 toxin. This novel peptide is composed of 42 amino acids with a MW of 4792.88 Da, folded by four disulfide bonds and it is classified as member number 10 of the gamma-KTx1 toxin family. CmERG1 inhibits hERG1 currents with an IC50 of 3.4 +/- 0.2 nM. Despite its 90.5% identity with toxin gamma-KTx1.1, isolated from Centruroides noxius, CmERG1 completely blocks hERG1 current, suggesting a more stable plug of the hERG channel, compared to that formed by other gamma-KTx.

Automated summary

This study investigated a venom component from Centruroides margaritatus, CmERG1, which inhibits hERG1 channels completely. Despite its high similarity with another toxin, CmERG1 showed a stable plug effect on the hERG channel, distinguishing it from other gamma-KTx toxins.