α-Conotoxin EI

α-Conotoxin EI (CAS No. 170663-33-9) is a peptide toxin derived from the venom of the Atlantic fish-hunting cone snail Conus ermineus. It specifically targets nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels composed of multiple subunits widely distributed in the muscle and nervous systems, and mediate synaptic transmission and cellular signal transduction. α-Conotoxin EI binds to the subunit interfaces of nAChRs: at extremely low concentrations (0.2-10 nM) with brief exposure (2-15 s), it potentiates the responses of receptor subtypes such as α₁β₁γδ and α₄β₂ to acetylcholine; whereas at high concentrations (1-10 μM) with prolonged exposure (>30 s), it competitively blocks receptor function, with particularly significant effects on the α₁β₁γδ and α₃β₄ receptor subtypes. This dual action arises from its regulation of receptor conformations: stabilizing the activated conformation at low concentrations and occupying the ligand-binding site at high concentrations. By targeting specific nAChR subtypes, including α₁β₁γδ, α₄β₂, and α₃β₄, α-Conotoxin EI exhibits important research value in distinguishing neuronal receptor subtypes, studying synaptic transmission mechanisms, and developing therapeutic drugs for neurological diseases.

Reference:

[1] Martinez JS, Olivera BM, Gray WR, Craig AG, Groebe DR, Abramson SN, McIntosh JM. alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity. Biochemistry. 1995 Nov 7;34(44):14519-26.

[2] Park KH, Suk JE, Jacobsen R, Gray WR, McIntosh JM, Han KH. Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor. J Biol Chem. 2001 Dec 28;276(52):49028-33.

[3] López-Vera E, Aguilar MB, Schiavon E, Marinzi C, Ortiz E, Restano Cassulini R, Batista CV, Possani LD, Heimer de la Cotera EP, Peri F, Becerril B, Wanke E. Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share high-affinity potentiation and low-affinity inhibition of nicotinic acetylcholine receptors. FEBS J. 2007 Aug;274(15):3972-85.

[4] Ning J, Ren J, Xiong Y, Wu Y, Zhangsun M, Zhangsun D, Zhu X, Luo S. Identification of Crucial Residues in α-Conotoxin EI Inhibiting Muscle Nicotinic Acetylcholine Receptor. Toxins (Basel). 2019 Oct 16;11(10):603.

[5] Rybin MJ, O'Brien H, Ramiro IBL, Azam L, McIntosh JM, Olivera BM, Safavi-Hemami H, Yoshikami D. αM-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish. Toxins (Basel). 2020 Mar 21;12(3):197.