Acetylcholine receptors postsynaptic

The AMPA receptors for glutamate, the nicotinic acetylcholine receptor and the 5-HT3-receptor for serotonin are cation channels (Table 1). When they open, the major consequence is a sudden entry of Na+, depolarization and an excitatory postsynaptic potential (EPSP Fig. 1). 

In the venom of C. geographus and other fish-hunting species, the conotoxins isolated so far can be divided into three major classes (1-4) o -conotoxms which block neuronal calcium channels at the presynaptic terminus of the neuromuscular junction, a-conotoxins which inhibit the acetylcholine receptor at the postsynaptic terminus, and x-conotoxins which block Na channels on the muscle membrane. 

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). 

Neonicotinoids are potent broad-spectrum insecticides that exhibit contact, stomach and systemic activity. Acetamiprid, imidacloprid, nitenpyram, thiamethoxam and thiacloprid are representatives of the neonicotinoid insecticides (Figure 1). The mechanism of action is similar to that of nicotine, acting on the central nervous system causing irreversible blocking of postsynaptic nicotinic acetylcholine receptors (nAChR). Neonicotinoid insecticides are often categorized as antagonists of the... 

LaRochelle, W.J., and Froehner, S.C. (1986a) Determination of the tissue distributions and relative concentrations of the postsynaptic 43-kDa protein and the acetylcholine receptor in Torpedo. J. Biol. Chem. 261, 5270-5274. 

Mixture of neurotoxins that block the acetylcholine receptors. The /3-bungarotoxin is a pre-synaptic neural toxin, a-bungarotoxin is a postsynaptic neural toxin, and K-bungarotoxin is specific to the neuronal receptors in ganglions. They are obtained from the venom of the banded krait (Bungarus multicinctus). 

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... 

In the adrenal medulla and the ganglia of parasympathetic and sympathetic nerves, the neurotransmission is mediated by acetylcholine. On the postsynaptic membranes the transmitter activates the neuronal-type of the nicotinic acetylcholine receptor. This receptor type is in fact a sodium channel, its activation leads to a sodium influx and a membrane depolarization. A pharmacological interference at the... 

Sigma 2000 MVIIA/postsynaptic inhibition or blocking of Neurex (Elan nicotinic acetylcholine receptor, according to type Pharm.) Kohno 1995, and its synthetic version SNX-111... 

The nicotinic acetylcholine receptor is a protein of 290 kD that occins in chemical synapses where conummication between nerve cells and muscle cells takes place. Binding of acetylcholine to the receptor induces opening of the ion chaimel, which is a part of the receptor. Passage of Na and ions through the receptor takes place and depolarization of the postsynaptic cell occurs. The depolarization represents a signal that-according to the nature of the postsynaptic cell—is processed in various ways. 

Fig. 16.13. Pore structure of the acetylcholine receptor, based on electron microscopy studies. a) Electron density map of the acetylcholine receptor of the postsynaptic membrane of the electric organ of the ray Torpedo californicus, based on electron microscopy studies. The receptor has a long funnel-like structure in the extracellular region, which narrows at the center of the pore. A smaller funnel structure is observed in the cytoplasmic region of the receptor. Another protein is situated on the cytoplasmic side. The long arrow indicates the direction of ion passage and the small arrow shows the postulated binding site for acetylcholine, b) Schematic representation of the acetylcholine receptor with the M2 hehx as the central block in the ion channel. According to Unwin, (1993).

Serotonin is involved in a number of diverse activities, including an important role in emesis. Four main subtypes of 5-HT receptor have been discovered, each having specific roles. The 5-HT3 receptor is a ligand-gated ion channel similar to the muscarinic acetylcholine receptor, whereas 5-HTl, 5-HT2 and 5-HT4 are G protein-coupled receptors. 5-HT3 receptors are located both pre-and postsynaptically on neurones in the central and peripheral nervous systems. In the CNS they are present in high concentrations in the area postrema, and peripherally in the upper GIT. 

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. 

Pesticides derived from natural sources include nicotine, rotenone, and pyrethrum. Nicotine is obtained from the dried leaves of Nicotiana tabacum and N rustica. It is rapidly absorbed from mucosal surfaces the free alkaloid, but not the salt, is readily absorbed from the skin. Nicotine reacts with the acetylcholine receptor of the postsynaptic membrane (sympathetic and parasympathetic ganglia, neuromuscular junction), resulting in depolarization of the membrane. Toxic doses cause stimulation rapidly followed by blockade of transmission. These actions are described in Chapter 7. Treatment is directed toward maintenance of vital signs and suppression of convulsions. 

One of the best-understood examples of a ligand-gated receptor channel is the nicotinic acetylcholine receptor (see Fig. 11-51). The receptor channel opens in response to the neurotransmitter acetylcholine (and to nicotine, hence the name). This receptor is found in the postsynaptic membrane of neurons at certain synapses and in muscle fibers (myocytes) at neuromuscular junctions. 

Acetylcholine released by an excited neuron diffuses a few micrometers across the synaptic cleft or neuromuscular junction to the postsynaptic neuron or myocyte, where it interacts with the acetylcholine receptor and triggers electrical excitation (depolarization) of the receiving cell. The acetylcholine receptor is an allosteric protein with two high-affinity binding sites for acetylcholine, about 3.0 nm from the ion gate, on the two a... 

Perhaps the most well-known example is the acetylcholine receptor located on the postsynaptic membrane of the neuromuscular junction49 56 (Fig. 4-1). When bound by acetylcholine molecules, the receptor activates and opens a pore through the cell membrane, thereby increasing the permeability of the muscle cell to sodium.38 56 This action results in depolarization and excitation of the cell because of sodium influx. Another important example of a receptor-ion channel system is the gamma-aminobutyric acid (GABA)-benzodiazepine-chloride ion channel complex found on neuronal membranes in the central nervous sys-... 

Neurotransmitters are recognized by receiving neurons, neuromuscular junctions, or end effector organs via receptors that lie on the postsynaptic membrane. Receptors are generally selective for the neurotransmitter that they bind. The type of signaling that is characteristic of a given neurotransmitter is usually the result of the form of receptor to which it binds. For example, some receptors, like the nicotinic acetylcholine receptor found in neuromuscular junctions, are ion channels. The stimulation of the nicotinic... 

---