Nicotinic acetylcholine receptor channel

Abassy, M.A., M.E. Eldefrawi, and A.T. Eldefrawi. 1983. Pyrethroid action on the nicotinic acetylcholine receptor/channel. Pestic. Biochem. Physiol. 19 299-308. 

Eldefrawi, A. T., Miller, E. R., Murphy, D. L., and Eldefrawi, M. E. (1982) (3H)Phencyclidine interactions with the nicotinic acetylcholine receptor channel and its inhibition by psychotropic, antipsychotic, opiate, antidepressant, antibiotic, antiviral and antiarrhythmic drugs. Mol. Pharmacol., 22 72-81. 

Anderson DJ, Puttfarcken PS, Jacobs 1, Faltynek C (2000) Assessment of nicotinic acetylcholine receptor-mediated release of [ H]-norepinephrine from rat brain slices using a new 96-well format assay. Neuropharmacology 39 2663-2672 Anney RJ, Olsson CA, Lotfi-Miri M, Patton GC, Williamson R (2004) Nicotine dependence in a prospective population-based study of adolescents the protective role of a functional tyrosine hydroxylase polymorphism. Pharmacogenetics 14 73-81 Auerbach A, Akk G (1998) Desensitization of mouse nicotinic acetylcholine receptor channels. 

Figure 6 shows the proposed subunit assembly structure of the nicotinic acetylcholine receptor channel." The inner wall of the lower half part is surrounded by hydroxyl side chains from Ser and Thr, and by carboxylates or amides from Asp, Glu, and Gin at the mouth. Furthermore, a Lys residue seems to offer ion pairing with the carboxylate at the mouth. Considering the possibly similar stabilizing effect of ether and hydroxyl groups to cations, the proposed artificial supramolecular channel could be regarded as a good model of the acetylcholine receptor channel, which selects cations over anions, but does not discriminate between alkali metals. 

Figure 6. Proposed inner wall structure of the nicotinic acetylcholine receptor-channel composite from a2pY8 subunit assembly. The channel mouth is constructed from charged amino acids and their amides such as Asp, Glu, and Gin. A Lys is located at just the inner mouth. The lower half is covered by the amino acids having hydroxyl such as Ser and Thr, while the upper half is lined up with hydrophobic residues such as Leu, Val, Ala, lie, and Phe.

Pharmacologically, the histrionicotoxins affect at least three classes of channels in nerve and muscle. The first class of channels are the receptor-regulated channels, in particular the nicotinic acetylcholine receptor-channel, where histrionicotoxins, in a time- and stimulus-dependent man-... 

Labarca C, Schwarz J, Deshpande P, Schwarz S, Nowak MW, Fonck C, Nashmi R, Kofuji P, Dang H, Shi W, Fidan M, Khakh BS, Chen Z, Bowers BJ, Boulter J, Wehner JM, Lester HA (2001) Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopamineigjc deficits and increased anxiety. Proc Natl Acad Sd USA 98 2786-2791 Lamb PW, Melton MA, Yakel JL (2005) Inhibition of neuronal nicotinic acetylcholine receptor channels expressed in Xenopus oocytes by beta-amyloid 1-42 peptide. J Mol Neurosd 27 13-21... 

The aqueous domains are large enough to permit rapid access of the ions to the membrane channel, but sufficiently constrained so that ion selectivity effects, as the result of charge interactions, are likely to be important. The nicotinic acetylcholine receptor channel is highly selective for cations. However, there is less specificity among the cations. The permeability sequence for monovalent cations, Cs > Rb > > Na" > Li suggests weak interactions... 

Nagata. K., Huang, C. S., Song, J, H, and Narahashi, T. (1997), Direct actions of anticholinesterases on the neuronal nicotinic acetylcholine receptor channels. Brain Res. 769, 211-218. 

The open and closed conformations on binding ligands to the nicotinic acetylcholine receptor channel were already trapped and observed by electron microscopy. Here again, the cooperative binding of ligands induces large rotational movements of the pore-defining subunit-. 

A series of potent alkaloids were first isolated from den-drobatid frogs of western Colombia and northwestern Ecuador, but are now known to be more widespread in distribution. These alkaloids affect at least three classes of channels in nerve and muscle. The first two are receptor-regulated channels, in particular the nicotinic acetylcholine receptor channel. The histrionicotoxins are noncompetitive blockers of this receptor-channel complex (Daly et al, 1993). The second class of channels are the voltage-dependent sodium channels. Histrionicotoxins reduce conductances in a manner reminiscent of local anesthetics (Daly et al., 1993). Despite these effects, these alkaloids have relatively low toxicity (Daly et al., 1993). 

L. P. Zanello, E. Aztiria, S. Antollini, F. J. Barrantes, Nicotinic acetylcholine receptor channels are influenced by the physical state of their membrane environment, Biophys. J. 70(1996)2155. 

Gessner W, Takahashi K, Witkop B, Brossi A, Albuquerque EX. Probes for a regulatory site on the nicotinic acetylcholine receptor-channel. Synthesis of ( )-7-debutylperhydrohistrioni-cotoxin, ( )-2-depentyl-7-debutylperhydrohistrionicotoxin, and their analogues. Helv. Chim. Acta 1985 68 49-55. 

Histrionicotoxin noncompetitively inhibits nicotine-stimulated secretion of catecholamines from adrenal medulla cells 164), suggesting similar interactions of the alkaloid with the nicotinic acetylcholine receptor channel complex in both adrenal medulla and in muscle., ... 

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