Acetylcholine Receptor AChR

Radioiodinated derivatives have been prepared to define more closely the target site of a-conotoxins on the acetylcholine receptor (R. Myers, unpublished data). In membrane preparations from Torpedo electroplax, photoactivatable azidosalicylate derivatives of a-conotoxin GIA preferentially label the p and 7 subunits of the acetylcholine receptor. However, when the photoactivatable derivative is cross-linked to detergent solubilized acetylcholine receptor (AChR), only the 7 subunit is labeled. Since snake a-neurotoxins mainly bind to the a subunits of AChR and a-conotoxins compete directly with a-bungarotoxin, the cross-linking results above are both intriguing and problematic. 

In order to understand the exact mechanism of the neurotoxic action, it is important to know the secondary structure of the neurotoxins as well. It is now known that postsynaptic neurotoxins attach to the a-subunits of acetylcholine receptor (AChR). 

When a nerve-muscle preparation is stimulated in the presence of a sea snake neurotoxin, there is no twitch. However, when the muscle itself is stimulated directly in the presence of a neurotoxin, the muscle contracts. This means that neurotoxin does not inhibit the muscle itself. Moreover, postsynaptic neurotoxin does not inhibit the release of acetylcholine from the nerve ending. Therefore, the site of snake toxin inhibition must be in the postsynaptic site 20). Later it was shown that a neurotoxin strongly binds to the acetylcholine receptor (AChR). 

The acetylcholine receptor (AChR) of Torpedo electric organ is also a PCP "receptor." However, this nicotinic AChR has about one-tenth the affinity for PCP than that of the rat brain PCP receptor [K0.5 = 0.3 pM, versus = 4-6 pM for Torpedo (Heidmann et al. 1983 flaring et al. 1984)]. Moreover, the nicotinic AChR has subunits of MR<66 kD, and these are the subunits that are specifically labelled with 3H-Az-PCP in the Torpedo electroplax membranes (Heidmann et al. 1983 Haring and Kloog 1984 Haring et al. 1984). These data indicate that the nicotinic AChR-PCP receptor differs from the rat brain PCP receptor. Furthermore, our findings are... 

Tyrosine phosphorylation has a role in the formation of the neuromuscular synapse. For instance, the acetylcholine receptor (AChR) is concentrated at the postsynaptic membrane of the neuromuscular junction at a density of 10,000 receptors/pm2, which is about three orders of magnitude higher than that of the extrasynaptic region... 

The isolation of the nicotinic acetylcholine receptor glycoprotein was achieved almost simultaneously in several laboratories (those of Changeux, O Brien, Brady, and Eldefrawi) and was helped tremendously by the discovery that the electric organ (elec-troplax) of the electric eel (Electrophorus electricus, an inhabitant of the Amazon River) and related species, as well as the electroplax of the electric ray Torpedo tnar-morata) of the Atlantic Ocean and the Mediterranean Sea, contains acetylcholine receptors (AChR) in a much higher concentration than, for instance, in human neuromuscular endplates or brain tissue. 

The elucidation of the amino acid sequence of many channels now allows structural and phylogenetic comparisons. The nicotinic acetylcholine receptor (AchR) Na" -channel,... 

Each of their receptors transmits its signal across the plasma membrane by increasing transmembrane conductance of the relevant ion and thereby altering the electrical potential across the membrane. For example, acetylcholine causes the opening of the ion channel in the nicotinic acetylcholine receptor (AChR), which allows Na+ to flow down its concentration gradient into cells, producing a localized excitatory postsynaptic potential—a depolarization. 

Amino acid analyses of acetylcholine esterase (AchE) and acetylcholine receptor (AchR) of Electrophorus electicus have been performed by various investig-... 

Use of Toxin Binding to Purify a Channel Protein a-Bungarotoxin is a powerful neurotoxin found in the venom of a poisonous snake (Bungarus multicinctus). It binds with high specificity to the nicotinic acetylcholine receptor (AChR) protein and prevents the ion channel from opening. This interaction was used to purify AChR from the electric organ of torpedo fish. 

Acetylcholine receptors (AChRs) are of two types muscarinic (mAChR) and nicotinic (nAChR) based on the agonist activities of the natural alkaloids, muscarine and nicotine, respectively. These receptors are functionally different. The muscarinic type being G-protein coupled receptors mediate a slow metabolic response via second messenger cascades, while the nicotinic type are ligand-gated ion channels, which mediate a fast synaptic transmission of the neurotransmitter. Skeletal muscles are enriched with nAChRs and are devoid of mAChRs. 

The methodology discussed above has been used in the resonance assignment and to determine the backbone conformation of a uniformly N-labeled M2 transmembrane peptide of nicotinic acetylcholine receptor (AChR), one of the major excitatory neurotransmitters in the brain. By comparing with spectra from selectively and specifically N-labeled M2 peptides and using the sequential (z to z-Fl) cross peaks in the spin exchange spectra, all the resonances from the M2 peptide were assigned. 

Myasthenia gravis is a neurological disease of autoimmune origin. The basic defect is the reduction of ificotinic acetylcholine receptors (AChR) at the neuromuscular junction, resulting in inadequate transmission through the neuromuscular junction and hence the clinical syndrome of weakness, frequently worsened by exercise or effort. 

By the time of innervation at G16, the acetylcholine receptors (AChRs) which had been scattered along the length of the immature muscle fibers, cluster at the areas which will become the neuromuscular junction (Anderson and Cohen, 1977), a phenomenon that is at least partially dependent upon the release of agrin from the approaching axon terminal (McMahan et al., 1980). 

Acetylcholine receptor acetylcholine receptor (AChR) is a nicotinic musde receptor, a pentamer ion channel with a prominent extracellular domain, mediating the... 

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