This gating-modifier toxin shows an important inhibitory activity on sodium channels (PubMed:29723257). It is very active on Nav1.7/SCN9A (IC(50)~0.6 nM), and also shows activity on Nav1.3/SCN3A (IC(50)=292 nM), Nav1.4/SCN4A (IC(50)=2.2-159 nM), and Nav1.5/SCN5A (IC(50)=2.3-2.9 uM) (PubMed:25055801, PubMed:29723257). It has also been shown to inhibit tetrodotoxin (TTX)-resistant (IC(50)=27.6 nM) and TTX-sensitive (IC(50)=30.2 nM) sodium channels in rat dorsal root ganglion neurons (PubMed:17157888). Lower inhibitory activity has also been shown on potassium channels: Kv4.2/KCND2 (IC(50)=604.2 nM), Kv4.3/KCND3 (IC(50)=425.1 nM), and Kv2.1/KCNB1 (IC(50)=14.3 uM) (PubMed:17157888, PubMed:20571743, PubMed:17150181). It binds to phospholipid membranes. Like its analog AM-8145, it may act by interacting only with the second voltage-sensor domain of Nav1.7/SCN9A (Probable). Expressed by the venom gland. The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. Does not inhibit Kv1.2/KCNA2, Kv1.3/KCNA3, and Kv1.4/KCNA4 channels (PubMed:17157888). Shows an extremely weak inhibition on Kv4.1/KCND1 (PubMed:17150181). The analog AM-8145 has a propargylglycine (Pra) N-terminally inserted, a norleucine (Nle) that replaces Met-59 (Met-6), and a Glu instead of Ile-81 (Ile-28). This analog potently blocks Nav1.7/SCN9A (IC(50)=0.5 nM) by interacting only with its second voltage-sensor domain (PubMed:29723257). It is 30- to 120-fold less active on TTX-sensitive sodium channels, and shows no or very low activity on TTX-resistant sodium channels (PubMed:29723257). The analog AM-0422 has a beta-cyanoalanine (CyA) N-terminally inserted, a norleucine (Nle) that replaces Met-59 (Met-6), a propargylglycine (Pra) instead of Glu-70 (Glu-17), and a Glu instead of Ile-81 (Ile-28). This analog potently blocks Nav1.7/SCN9A (IC(50)=0.8 nM) (PubMed:29723257). It also potently blocks TTX-sensitive sodium channels in mouse and rat DRG neurons (IC(50)=9-27 nM) (PubMed:29723257). It also specifically blocks capsaicin-induced rat DRG neuron action potential firing (PubMed:29723257). In addition, it specifically blocks mechanically-induced C-fiber action potential firing from afferent nerve terminals (PubMed:29723257). The analog AM-8394 has a propargylglycine (Pra) N-terminally inserted, a norleucine (Nle) that replaces Met-59 (Met-6), and Glu residues instead of Leu-72 (Leu-19) and Ile-81 (Ile-28) (PubMed:29723257). This analog show a weak inhibitory activity on Nav1.7/SCN9A (IC(50)>1 uM) (PubMed:29723257). It does not show activity on TTX-sensitive sodium channels in mouse and rat DRG neurons (PubMed:29723257). As a consequence, it can be used as a negative control peptide. Belongs to the neurotoxin 30 (phrixotoxin) family.