It was recently discovered that Ssm Spooky Toxin (SsTx) with 53 residues serves as a key killer factor in red-headed centipede’s venom arsenal, due to its potent blockage of the widely expressed KCNQ channels to simultaneously and efficiently disrupt cardiovascular, respiratory, muscular, and nervous systems, suggesting that SsTx is a basic compound for centipedes’ defense and predation. Here, we show that SsTx also inhibits K_V1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking K_V7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block K_V7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on K_V1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of K_V1.3 expression. The results further suggest that SsTx is a key molecule for defense and predation in the centipedes’ venoms and it evolves efficient strategy to disturb multiple physiological targets.

• Centipede
• KV1.3
• KV7
• SsTx
• toxin

• Animals
• Arthropod Venoms/pharmacology
• Arthropods
• CHO Cells
• Cricetulus
• Cytokines/metabolism
• HEK293 Cells
• Humans
• KCNQ Potassium Channels/antagonists & inhibitors
• KCNQ Potassium Channels/physiology
• Kv1.3 Potassium Channel/antagonists & inhibitors
• Kv1.3 Potassium Channel/physiology
• Potassium Channel Blockers/pharmacology
• T-Lymphocytes/drug effects
• T-Lymphocytes/metabolism

The work showed that centipede venom can cause disorders in cardiovascular, respiratory, and nervous systems. The cardiovascular toxicity of the venom comes mostly from a peptide toxin SsTx, which blocks the KCNQ family of potassium channels. Retigabine, a KCNQ channel opener, neutralizes centipede venom toxicity, and thus could be used to treat centipede envenomation.

Centipedes can subdue giant prey by using venom, which is metabolically expensive to synthesize and thus used frugally through efficiently disrupting essential physiological systems. Here, we show that a centipede (Scolopendra subspinipes mutilans, ∼3 g) can subdue a mouse (∼45 g) within 30 seconds. We found that this observation is largely due to a peptide toxin in the venom, SsTx, and further established that SsTx blocks KCNQ potassium channels to exert the lethal toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the toxicity of a centipede’s venom. The study indicates that centipedes’ venom has evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and nervous systems by targeting the broadly distributed KCNQ channels, thus providing a therapeutic strategy for centipede envenomation.

• KCNQ
• SsTx
• centipede
• toxicity

The primary purpose of this article was to review the current literature regarding the clinical consequences of centipede envenomation in humans, in order to determine whether the bite of these arthropods is neurotoxic to humans or not. A thorough search of the literature regarding the clinical consequences of centipede bites in humans was applied, with great respect to neurological symptoms potentially caused by such bites. Centipede bite commonly causes only local reactions, which usually resolve within a few days without sequelae. The patients in the majority of centipede envenomations describe a painful but benign syndrome. However, mild constitutional symptoms are relatively frequent. Remarkably, centipedes can rarely cause severe systematic reactions such as anaphylaxis or even hypotension and myocardial ischemia. Factors such as patient age, comorbidity, anatomic site of envenomation, and size/species of centipede should be considered when evaluating a centipede envenomation victim. According to the current literature, the centipede bite does not seem to be neurotoxic to humans. However, it commonly causes symptoms mediated by the nervous system. These include local and generalized symptoms, with the first dominated by sensory disturbances and the second by non-specific symptoms such as headache, anxiety and presyncope. Based on our results, the answer to our study’s question is negative. The centipede bite is not neurotoxic to humans. However, it commonly causes symptoms mediated by the nervous system, which include primarily local pain and sensory disturbances, as well as generalized non-specific symptoms such as headache, anxiety and vagotonia.

• Centipedes
• Pain
• Sensory disturbances
• Envenomation
• Scolopendra