, Alpha-conotoxin Vc1A
Also Known as
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).