Neuromuscular junctions nAChRs

A classic example of a ligand-gated ion channel from the cys-loop superfamily is the nAChR. The nicotinic AChRs are named so because they can be activated by the tobacco alkaloid nicotine in the same way they are activated by ACh. It should be mentioned that the muscarinic A.ChR s, which respond to the alkaloid muscarine, are not ion channels, and therefore not discussed in this chapter. The nAChR is made up of five subunits (al, pi, 7, 5, and e) with two binding sites for ACh (Figures 16.6B and 16.9). The nAChRs are expressed in nerves and skeletal muscle (but not smooth muscle) and play an important role in the fast synaptic transmission in synaptic neuronal-neuronal and neuromuscular junctions. nAChR is a nonselective cation channel that allows the flow of many cations, but not anions. After ACh binds to the nAChR it allows Na" " and also Ca " ", to flow down their electrochemical gradient into the cell, which depolarizes the cell membrane and generates an action potential (Figure 16.6B). 

The simplest agonist mechanism that can be used to describe activation of the ligand-gated ion-channel receptors is that first suggested by del Castillo and Katz (1957) for activation of nAChRs at the neuromuscular junction ... 

Acetylcholine (ACh) is an example of an endogenous neurotransmitter that binds to more than one receptor type, the nicotinic acetylcholine receptor (nAChR) which preferentially binds nicotine and the muscarinic receptor which binds muscarine, a mushroom alkaloid. The latter is a G protein-coupled receptor while the nACh receptor is an excitatory ligand-gated ion channel that transports Na-i- ions. Nicotinic cholinergic receptors are found in the CNS, autonomic ganglia, and at the neuromuscular junction of skeletal muscles. They are a possible target for anaesthetics. 

The nAChRs are defined by the alkaloid nicotine and possess a diverse pharmacological profile. This is due to the fact that they are located peripherally at the neuromuscular junctions, ganglia, and parasympathetic fibers where they are composed of four subunits (a ... 

Nicotinic receptors (nAChRs Fig. 30-23) of the type found in neuromuscular junctions are most frequently isolated from the electric organs of the electric... 

Similar nAChRs are also found in the brain.621 631 632 However, they are not identical but have at least 17 differing amino acid sequences (al-alO, (31-(34, y, 8, and e). The neuromuscular junction receptor (muscle type) from fish is described as (al)2 (31 my / S.626 The brain contains homopentamers of subunits a7, a8, and a9 as well as various heteropentamers. The various forms possess different affinities for acetylcholine and for antagonists such as nicotine.633 634 In the brain the highest affinity for nicotine is shown by an a4 32 form, which represents over 80% of the nAChR in mammalian brain.634 635 Knockout mice in which the (32 subunit gene has been deleted lose their sensitivity to nicotine. 

At the neuromuscular junction, nicotinic function is enhanced by inhibition of AChE. However, unlike muscle nAChRs, some neuronal nAChRs, particularly those bearing the a7 subunit, recognize both acetylcholine and its metabolite choline as full agonists (Pereira et al., 2002). Therefore, cholinesterase inhibition may not necessarily enhance functions mediated by these nAChRs. In fact, cholinesterase inhibitors do not affect a7 nAChR-mediated synaptic transmission evoked by low-frequency stimulation of cholinergic fibers in chick cUiary ganglia (Zhang et al., 1996). 

Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels that are found in abundance at the neuromuscular junction, and are widely distributed throughout the central and peripheral nervous systems. They comprise five subunit proteins that combine to form a cation permeable pore at the cell surface. In neuronal tissues, multiple nAChR subtypes may be assembled from a diverse array of subunits (a2-a9 32-p4) and their... 

As mentioned above, the classic experiments by Langley with the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction has led to the... 

Similar nAChRs are also found in the brain. However, they are not identical but have at least 17 differing amino acid sequences (al-alO, pi- 34, y, 8, and e). The neuromuscular junction receptor (muscle type) from fish is described as (al)2 pl y/e 5. ... 

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