Neuromuscular endplate

NM receptors—nicotinic-muscular receptors (found in skeletal muscle neuromuscular endplates)... 

Acetylcholine (ACh) has been known as a neurotransmitter since the mid-1920s. In fact, the demonstration that acetylcholine is the Vagusstoff ( vagus-substance ) released from the vagus nerve to modulate heart function was the first proof for the chemical mediation of nerve impulses (Loewi and Navratil, 1926). In the peripheral nervous system, ACh is found as the neurotransmitter in the autonomic ganglia, the parasympathetic postganglionic synapse, and the neuromuscular endplate. 

As do most neuronal systems, cholinergic receptors show multiplicity, and we distinguish between nicotinic and muscarinic receptors, which differ in many respects. Whereas acetylcholine (4.1) binds to both types of receptors, the plant alkaloids nicotine (4.2) and muscarine (4.3) trigger a response only from nicotinic or muscarinic cholinergic receptors, respectively. Nicotinic receptors are found in all autonomic ganglia (i.e., in the sympathetic system as well as the parasympathetic) and at the neuromuscular endplate of striated muscle. Muscarinic receptors occur at postganglionic... 

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 nicotinic AChRs in the ganglion cell and in the neuromuscular endplate are different. The difference probably consists of dissimilar accessory sites. In addition, the neuromuscular site can accommodate not only compounds with an N+-N+ distance of 10 atoms but also those with an N-N+ distance of 16 atoms. 

Based on electromyographic (EMG) findings from OP-poisoned patients and experimental studies on laboratory animals, scientists have found that the defect in IMS is at the neuromuscular endplate and postsynaptic level, but the effects of neural and central components in producing muscular weakness have not been ruled out. EMG findings in the early... 

The axon leads to a knob-shaped swelling (synaptic button) if the nerve is communicating with another nerve. Alternatively, if the nerve is communicating with a muscle cell, the axon leads to what is known as a neuromuscular endplate, where the nerve cell has spread itself like an amoeba over an area of the muscle cell. 

Within the synaptic button or neuromuscular endplate there are small globules... 

Once the action potential reaches the synaptic button or the neuromuscular endplate, it causes an influx of calcium ions into the cell and an associated release of neurotransmitter into the synaptic gap. The mechanism of this is not well understood. 

Up to the present, the most thoroughly investigated are the vertebrate nicotinic acetylcholine receptors. They are not only found in the brain, on the neuromuscular endplates of the somatic nervous system, and in the ganglia of the autonomic nervous system, but also on nonexcitable cells like keratinocytes. This more recent paradigm shift indicates that even more scientific revelations are to be expected in clarifying the underlying signaling mechanisms within this sophisticated system. [126]... 

Evolution has spawn over time a large variety of nicotinic acetylcholine receptor subtypes. The receptor of the electric ray consists of two identical aj-subunits and another three different, pj, y and 6 subunits. The structure of the nicotinic acetylcholine receptor at the neuromuscular endplate is similarly configured. 

The a-conotoxins of cone snails, twelve to sixteen amino acids in length, are among the smallest known peptidic, nAChR antagonists (Fig. 8.40). [132,133] These bind with remarkable selectivity at the different subtypes of neuronal nicotinic receptors and at those of the neuromuscular endplate. The a-conotoxin Mil (GlyCysCysSerAsnProValCysHisLeuGluHisSerAsnLeuCysNH2 [134]) from Conus magnus, for instance, inhibits the (a3)2(P2)3"teceptor in the low to sub-nanomolar region, with a > 200-fold selectivity over related receptors. 

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