Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin inhibits inactivation of Nav1.6/SCN8A (EC(50)=3.1 uM) and drosophila DmNav1 (EC(50)=1.17 uM) (PubMed:21969612, Ref.2, PubMed:33051988). It also shows a weak inhibition of inactivation on Nav1.2/SCN2A Nav1.3/SCN3A, and Nav1.7/SCN9A (PubMed:21969612, PubMed:33051988). The toxin (1 uM) does not significantly shift the midpoint of activation at the two channels, but induces a significant depolarizing shift in the V(1/2) of inactivation of the channels (PubMed:21969612). The toxin has also been shown to dose-dependently stimulates intracellular signaling in DRG neurons through activation of two kinases (type II protein kinase A (PKA-II) and MAP kinases 1/3 (MAPK1/MAPK3)) (PubMed:33051988). Nav1.2/SCN2A is strongly suggested to be the target channel predominantly involved in this activation (PubMed:33051988). In vivo, the toxin induces a dose-dependent thermal hyperalgesia lasting 30-45 minutes (PubMed:33051988). Expressed by the venom gland. Has the structural arrangement of an alpha-helix connected to antiparallel beta-sheets by disulfide bonds (CS-alpha/beta). A labile and variable specificity module composed of 3 loops determines the selectivity of scorpion Nav alpha-toxins. In this toxin, the specificity module consists of: an N-terminal loop following beta-1 and up to the first cysteine residue (residues 27-31), the tip of the beta-2-beta-3 hairpin (58-62), and a C-terminal region (75-83). C-terminal amidation does not appear to play an important role in activity, since the non-amidated recombinant toxin and the native toxin (which is amidated) show similar activities on all sodium channels tested. LD(50) is 5.8 mg/kg by subcutaneous administration into mice. Shows no effect on Nav1.4/SCN4A, Nav1.5/SCN5A and Nav1.8/SCN10A (PubMed:21969612, PubMed:33051988). Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.