Recombinant Androctonus mauretanicus mauretanicus Alpha-toxin Amm8

Function

Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission (PubMed:12911331). The toxin principally slows the inactivation process of TTX-sensitive sodium channels (PubMed:23685008). It discriminates neuronal versus muscular sodium channel, as it is more potent on rat brain Nav1.2/SCN2A (EC(50)=29 nM) than on rat skeletal muscle Nav1.4/SCN4A (EC(50)=416 nM) (PubMed:12911331). It also shows a weak activity on Nav1.7/SCN9A (EC(50)=1.76 uM) (PubMed:23685008). In vivo, the toxin produces pain hypersensibility to mechanical and thermal stimuli (PubMed:23685008). It also exhibits potent analgesic activity (when injected intraperitoneally), increasing hot plate and tail flick withdrawal latencies in a dose-dependent fashion (PubMed:20619318). This paradoxical analgesic action, is significantly suppressed by opioid receptor antagonists, suggesting a pain-induced analgesia mechanism that involves an endogenous opioid system (PubMed:20619318). This led to hypothesis that pain relief induced by peripheral administration of Amm VIII may result from sensitization of primary afferent neurons and subsequent activation of an opioid-dependent noxious inhibitory control (PubMed:20619318)

Subcellular Location

Secreted

Tissue Specificity

Expressed by the venom gland

• Alami M. et al. Characterization of Amm VIII from Androctonus mauretanicus mauretanicus: a new scorpion toxin that discriminates between neuronal and skeletal sodium channels. — Biochem. J. (2003)
• Alami M. et al. Genomic characterisation of the toxin Amm VIII from the scorpion Androctonus mauretanicus mauretanicus. — Toxicon (2006)
• Oukkache N. et al. New analysis of the toxic compounds from the Androctonus mauretanicus mauretanicus scorpion venom. — Toxicon (2008)
• Martin-Eauclaire M.F. et al. Involvement of endogenous opioid system in scorpion toxin-induced antinociception in mice. — Neurosci. Lett. (2010)
• Abbas N. et al. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na[+] channels. — Pain (2013)