Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin (native toxin Vc1a; hydroxylated and gamma-carboxylated) blocks alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (IC(50)=62.9 nM) (PubMed:17804600). In contrast to the non-post-translationally modified analog Vc1.1, Vc1a does not inhibit high voltage-activated (HVA) calcium channel currents (PubMed:18945902). In vivo, in contrast to Vc1.1, Vc1a does not show analgesic effects in rat models of neuropathic pain (PubMed:17804600). The synthetic peptide Vc1.1 (a non-hydroxylated and non-gamma-carboxylated analog of Vc1a) has two types of targets. It blocks alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (on rat receptors, IC(50)=19-109 nM) (with preference for rat over human receptors) and inhibits high voltage-activated (HVA) calcium channel (Cav2.2, Cav2.3) currents by acting on GABA(B) receptors (GABBR1 and GABBR2) (IC(50)=1.7 nM) (PubMed:17101979, PubMed:17804600, PubMed:18945902, PubMed:19447885, PubMed:23566299, PubMed:26948522, PubMed:20533477, PubMed:23768016). It also shows moderate inhibition on alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) (IC(50)=140 nM) and alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) (IC(50)=980 nM) (PubMed:17101979). On alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR, it most likely interacts with the alpha-10(+)/alpha-9(-)interface of the receptor (PubMed:23566299). In vivo, it acts as a powerful analgesic in rat models of neuropathic pain (PubMed:17804600). Expressed by the venom duct. The cysteine framework is I (CC-C-C). Alpha4/7 pattern. Vc1.1 is described as having no post-translational modifications (except C-terminal amidation), whereas Vc1a contains a hydroxyproline at Pro-55 and a 4-carboxyglutamate at Glu-63 (and a C-terminal amidation) (PubMed:17101979, PubMed:17804600). Hydroxylation of Pro-55 is not important for inhibition of alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs, since [P6O]Vc1.1 (Pro-55 hydroxylated) shows similar inhibition than native toxin (IC(50)=99.1 nM) (PubMed:17804600). In contrast, hydroxylation of Pro-55 seems to impair inhibition of HVA calcium channel currents, since [P6O]Vc1.1 has no effect on HVA calcium channel currents (PubMed:18945902). In vivo, hydroxylation of Pro-55 seems to induce the loss of analgesic effects in rat models of neuropathic pain, since [P6O]Vc1.1 has no effect on mechanical allodynia (PubMed:17804600). Gamma-carboxylation of Glu-63 is not important for inhibition of alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs, since [E14gamma]Vc1.1 (carboxyglutamate at Glu-63) shows similar inhibition than native toxin (IC(50)=65.3 nM) (PubMed:17804600). In contrast, gamma-carboxylation of Glu-63 seems to impair inhibition of HVA calcium channel currents, since [E14gamma]Vc1.1 has no effect on HVA calcium channel currents (PubMed:18945902). Non-native isomers 'ribbon' (with disulfide connectivity C1-C4; C2-C3) and 'beads' (with disulfide connectivity C1-C2; C3-C4) of Vc1.1 also inhibit HVA calcium channel currents in rat DRG neurons (20-30% inhibition at 1 uM toxin) (PubMed:26948522). It has been shown that both reduced and alkylated Vc1.1 have no effect on HVA calcium channel currents. The observed activity can be attributed to specific isomers (PubMed:26948522). [C3S]Vc1.1(1-8) mutant is C-terminally amidated. Cyclic versions of Vc1.1 evoke significant anti-nociceptive actions in animal model of chronic visceral hypersensitivity (CVH), suggesting that they could be novel candidates for treatment of chronic visceral pain (CVP). The synthetic peptide Vc1.1 (a non-hydroxylated and non-gamma-carboxylated analog of Vc1a) shows weak inhibition on nAChRs composed of alpha-3-alpha-5-beta-2/CHRNA3-CHRNA5-CHRNB2 (IC(50)=7.2 uM), alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=5.5-7.3 uM), alpha-3-beta-4/CHRNA3-CHRNB4 (IC(50)=4.2 uM), alpha-3-alpha-5-beta-4/CHRNA3-CHRNA5-CHRNB4 (IC(50)>30 uM), alpha-4-beta-2/CHRNA4-CHRNB2 (IC(50)>30 uM), alpha-4-beta-4/CHRNA4-CHRNB4 (IC(50)>30 uM), rat alpha-7/CHRNA7 (IC(50)=7.1 uM) and alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND (IC(50)>30 uM) subunits. cVc1.1 is a cyclic peptide with inhibitory activity on alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (IC(50)=766 nM) and a high potency at inhibiting HVA calcium channels in mice DRG neurons (IC(50)=0.3 nM) (PubMed:20533477). Toxin cVc1.1[D11A; E14A] is a cyclic peptide with a very low inhibitory activity on alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (IC(50)>17 uM) and a high potency at inhibiting HVA calcium channels in mice DRG neurons (IC(50)=3.3 nM) (PubMed:29746088). Both of them show antinociceptive actions, with greater efficacy in a model of animal chronic visceral hypersensitivity (CVH) (PubMed:29194563, PubMed:29746088). Belongs to the conotoxin A superfamily.