α-Conotoxin EI

Product Name:α-Conotoxin EI

CAS No:170663-33-9

Purity:95%

Molar Mass:2093.4

Chemical Formula:C83H125N27O27S5

Storage:Store at -20 degrees Celsius

Sequence:RDXCCYHPTCNMSNPQIC

Target:neuromuscular nicotinic

Application:

α-Conotoxin EI is a peptide toxin isolated from the venom of the Conus ermineus snail. It is a potent and selective antagonist of muscle-type nicotinic acetylcholine receptors (nAChRs), particularly the α1β1γδ subtype found in skeletal muscles. This conotoxin is widely used in research to study neuromuscular transmission and receptor dynamics. By blocking these receptors, α-Conotoxin EI provides insights into the molecular mechanisms underlying conditions such as myasthenia gravis, muscular disorders, and neurotoxicity. Its high specificity also makes it valuable for exploring therapeutic targets for neuromuscular diseases and developing treatments for receptor-related dysfunctions.

Current Research:

α-Conotoxin EI is a peptide toxin derived from the venom of Conus ermineus, a marine cone snail species. It functions as a selective antagonist of nicotinic acetylcholine receptors (nAChRs), specifically targeting the α1β1γδ subtype found in skeletal muscle and the α3β4 subtype present in autonomic ganglia. This specificity renders it a valuable tool for investigating the physiological roles of these receptor subtypes and their involvement in neuromuscular transmission and autonomic regulation.

Structural Characteristics

α-Conotoxin EI is composed of a short sequence of amino acids stabilized by disulfide bonds, which confer a rigid three-dimensional structure essential for its high-affinity interaction with nAChRs. The precise conformation allows it to bind selectively to the receptor subtypes mentioned above, inhibiting their normal function.

Receptor Specificity and Binding Affinity

Studies have shown that α-Conotoxin EI inhibits the α1β1γδ nAChR subtype with an IC₅₀ of approximately 187 nM. It also acts as an inhibitor of the α3β4 nAChR subtype, though specific binding affinity data for this interaction are less well-defined. The ability of α-Conotoxin EI to block both muscle-type and certain neuronal nAChRs highlights its utility in dissecting the roles of these receptors in various physiological processes.

Mechanism of Action

By binding to the ligand-binding domain of nAChRs, α-Conotoxin EI competitively inhibits the action of acetylcholine, the endogenous neurotransmitter. This blockade prevents the opening of the receptor's ion channel, thereby inhibiting ion flux and subsequent cellular responses. In muscle-type nAChRs, this results in the suppression of neuromuscular transmission, while in neuronal nAChRs, it affects autonomic signaling pathways.

Research Applications

The selective inhibition properties of α-Conotoxin EI make it a valuable tool in neuropharmacological research:

Neuromuscular Studies: Utilized to investigate the role of muscle-type nAChRs in neuromuscular transmission and to explore potential therapeutic targets for conditions such as myasthenia gravis.

Autonomic Regulation: Employed to study the function of α3β4 nAChRs in autonomic ganglia, providing insights into autonomic nervous system disorders.

Drug Development: Serves as a lead compound for the design of novel therapeutics aimed at modulating nAChR activity in various neurological conditions.

Conclusion

α-Conotoxin EI is a potent and selective antagonist of specific nAChR subtypes, offering significant utility in the study of cholinergic signaling pathways. Its application in research continues to advance our understanding of nAChR function and holds promise for the development of targeted therapies for neuromuscular and autonomic disorders.

Reference:

Ning, J., Ren, J., Xiong, Y., Wu, Y., Zhangsun, M., Zhangsun, D., … & Luo, S. (2019). Identification of crucial residues in α-conotoxin EI inhibiting muscle nicotinic acetylcholine receptor. Toxins, 11(10), 603.