Acetylcholine receptor channel

Unwin, N. Acetylcholine receptor channel imaged in the open state. Nature 373 37-43, 1995. 

Unwin, N (1995) Acetylcholine receptor channel imaged in the open state. Nature 373 37-43. Unwin, N (2000) Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission. Phil. Trans. Roy. Soc. Lond. Ser. B 355 1813-1829. 

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. 

Albuquerque EX, Akaike A, Shaw KP, Rickett DL. The interaction of anticholinesterase agents with the acetylcholine receptor-channel complex. Fundam. Appl. Toxicol. 4 S27-S33, 1984. 

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. 

Akabas MH, Karlin A. 1995. Identification of acetylcholine receptor channel-lining residues in the Ml segment of the... 

Akabas MH, Stauffer DA, Xu M, Karlin A. 1992. Acetylcholine receptor channel structure probed in cysteine-substitution... 

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. 

Wilkie GI, Hutson P, Sullivan JP, Wonnacott S (1996) Pharmacological characterization of a nicotinic autoreceptor in rat hippocampal synaptosomes. Neurochem Res 21 1141-1148 Wilson GG, Karlin A (1998) The location of the gate in the acetylcholine receptor channel. Neuron 20 1269-1281... 

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.

Discussion of structure and function of the acetylcholine receptor channel. 

Along the same lines, an artificial ion channel was prepared by Montal and coworkers [33] using the TASP approach. In their work, a four a-helix bundle structure 67 was synthesized on a peptide template. The ion transport ability was well characterized and 67 turned out to have several similarities with the natural acetylcholine receptor channel they were mimicking. 

Koenen, M., Peter, C., Villarroel, A., Witze-mann, V. and Sakmann, B. (2005) Acetylcholine receptor channel subtype directs the innervation pattern of skeletal muscle. EMBO Rep 6, 570-576. 

Answer A hormone can be degraded by extracellular enzymes (such as acetylcholinesterase). The GTP bound to a G protein can be hydrolyzed to GDP. A second messenger can be degraded (cAMP, cGMP), further metabolized (IP3), or resequestered (Ca2 +, in the endoplasmic reticulum). A receptor can be desensitized (acetylcholine receptor/channel), phosphorylated/inactivated, bound to an arrestin, or removed from the surface ( -adrenergic receptor, rhodopsin). 

Gephyrotoxin (Cl9H29NO), in contrast to histrionicotoxin and pumilio-toxin C which are active in the acetylcholine receptor channel, is a muscarinic antagonist. 

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... 

How do ion chaimels, vital to a wide array of biological functions, operate at a molecular level We will examine three chaimels important in the propagation of nerve impulses the ligand-gated channel the acetylcholine receptor channel, which communicates the nerve impulse between certain neurons and the voltage-gated Na+ and K+ channels, which conduct the nerve impulse down the axon of a neuron. 

Like the acetylcholine receptor channel, the sodium channel also was purified on the basis of its ability to bind a specific neurotoxin. Tetrodotoxin, an organic compound isolated from the puffer fish, binds to sodium channels with great avidity (K nM). The lethal dose of this poison for an adult human being is about 10 ng. The sodium channel was first purified from the electric organ of electric eel, which is a rich source of the protein forming this channel. The isolated protein is a single chain of 260 kd. 

Fignre 13.16. Patch-Clamp Recordings of the Acetylcholine Receptor Channel. Patch-clamp recordings illustrate changes in the conductance of an acetylcholine receptor channel in the presence of acetylcholine. The channel undergoes frequent transitions between open and closed states. [Courtesy of Dr. D. Colquhoun and Dr. B. Sakmann.]... 

Figure 13.17. Schematic Representation of the Closed Form of the Acetylcholine Receptor Channel. In the closed state, the narrowest part of the pore is occluded by side chains coming from five helices. [Courtesy of Dr. Nigel Unwin.]...

Figure 13.18. Opening of the Acetylcholine Channel Pore. Large hydrophobic side chains (L) occlude the pore of the closed form of the acetylcholine receptor channel. Channel opening is probably mediated by the tilting of helices that line the pore. Large residues move away from the pore and small ones (S) take their place. [After N. Unwin. Neuron 3 (1989) 665.]...

Ligand-induced channel opening. The ratio of open to closed forms of the acetylcholine receptor channel containing zero, one, and two bound acetylcholine molecules is 5 x iq-6 1.2 x iq-3, and 14, respectively. 

Channel problems 2. The acetylcholine receptor channel can also undergo mutation leading to fast channel... 

Neher, E. Steinbach, J.H. Local anaesthetics transiently 41. block currents through single acetylcholine-receptor channels. J. Physiol. 1978, 227, 153-176. 

Ligand induced channel opening. The ratio of open to closed forms of the acetylcholine receptor channel containing zero. one. 

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