Skeletal muscles cholinergic system

There is considerable diversity among nicotinic acetylcholine receptors, and at least one source of this diversity is the multiplicity of acetylcholine receptor genes. Cholinergic-nicotinic receptors in skeletal muscle are different from those in autonomic ganglia and the central nervous system. 

The answer is d. (Hardman, pp 192-193.) Nicotine is a depolarizing ganglionic blocking agent that initially stimulates and then blocks nicotinic muscular (NM) (skeletal muscle) and nicotinic neural (NN) (parasympathetic ganglia) cholinergic receptors. Blockade of the sympathetic division of the autonomic nervous system (ANS) results in arteriolar vasodilation, bradycardia, and hypotension. Blockade at the neuromuscu-... 

Most blood vessels receive no direct innervation from the parasympathetic system. However, parasympathetic nerve stimulation dilates coronary arteries, and sympathetic cholinergic nerves cause vasodilation in the skeletal muscle vascular bed (see Chapter 6). Atropine can block this vasodilation. Furthermore, almost all vessels contain endothelial muscarinic receptors that mediate vasodilation (see Chapter 7). These receptors are readily blocked by antimuscarinic drugs. At toxic doses, and in some individuals at normal doses, antimuscarinic agents cause cutaneous vasodilation, especially in the upper portion of the body. The mechanism is unknown. 

Acetylcholine receptors are classified as either muscarinic cholinergic receptors or nicotinic cholinergic receptors. The alkaloid muscarine mimics the effects produced by stimulation of the parasympathetic system. These effects are postganglionic and are exerted on exocrine glands, cardiac muscle, and smooth muscle. The alkaloid nicotine mimics the actions of acetylcholine, which include stimulation of all autonomic ganglia, stimulation of the adrenal medulla, and contraction of skeletal muscle. 

Nicotiana tabacum, and lobeline, present in the dried leaves and tops of the herb, Lobelia inflata (13). Both nicotine and lobeline act as agonists on a specific type of acetylcholine receptor, the nicotinic cholinergic receptor. In mammals, nicotinic cholinergic receptors mediate cholinergic neurotransmission in skeletal muscles, autonomic ganglia, and the central nervous system. At these sites nicotine s action has two phases, excitation and depression. Insect central nervous tissues are rich in nicotinic cholinergic receptors (cf. 14), but their role in behavior is not well understood. 

Q4 The ganglionic transmitter of both divisions of the autonomic nervous system is acetylcholine. The major postganglionic neurotransmitter of the sympathetic nervous system is norepinephrine (noradrenaline), but a small number of structures are innervated by sympathetic, cholinergic fibres. These fibres release acetylcholine and the structures innervated include the sweat glands and blood vessels supplying skeletal muscle. In the parasympathetic system the postganglionic neurotransmitter is acetylcholine. 

Figure 7.6. Oiganisation of the autonomic nervous system, and the chemical types of synapses found within it. M Muscarinic, N Nicotinic cholinergic receptors D Dopaminergic, a, p Adrenergic receptors. (The irmervation of skeletal muscles by a-mo-toneurons is shown for comparison but not part of the autonomic system.) BBB Blood brain barrier. It protects the entire central nervous system, i.e. both the brain and the spinal cord.

Stimulus-evoked, calcium-dependent release of acetylcholine (ACh) from the cholinergic synapse normally occurs through the formation of a fusion complex between ACh-containing vesicles and the intracellular leaflet of the nerve terminal membrane (Amon et al., 2001). This synaptic vesicle fusion complex consists of several proteins of the SNARE family, including a 25 kDa synaptosomal associated protein (SNAP-25), vesicle-associated membrane protein (VAMP, or synaptobrevin), and the synaptic membrane protein syntaxin. Other SNARE proteins have been identified as components of membrane transport systems in yeast and mammals but have not been implicated as targets for BoNTs. Meanwhile, type A and E neurotoxins cleave SNAP-25 while types B, D, F, and G act on VAMP and type C1 toxin cleaves both syntaxin and SNAP-25. Neurotoxin-mediated cleavage of any of these substrates disrupts the processes involved in the exocytotic release of ACh and leads to flaccid paralysis of the affected skeletal muscles. 

Furthermore, it was observed that the oxime HI-6 might show direct pharmacological effects in the cholinergic nervous system in skeletal muscles. It has been found that HI-6 reduces the miniature endplate potentials and increases the quantal content by a dose-dependent decrease in the miniature endplate potential amplitude (Melchers et al., 1991). Other possible explanations have been suggested for oximes at other targets in the nervous system, such as... 

Sympathetic cholinergic system causes vasodilatation In skeletal muscle, but this is not Involved in most physiological responses. 

The mechanism is the same as before, but the phosphorylated adduct which is formed after the first three stages is extremely resistant to hydrolysis. Consequently, the enzyme is permanendy inactivated. Acetylcholine cannot be hydrolysed and as a result the cholinergic system is continually stimulated. This results in permanent contraction of skeletal muscle, leading to death. 

Anticholinesterase insecticides phosphorylate the active site of cholinesterase in all parts of the body. Inhibition of this enzyme leads to accumulation of acetylcholine at affected receptors and results in widespread toxicity. Acetylcholine is the neurohormone responsible for physiologic transmission of nerve impulses from preganglionic and postganglionic neurons of the cholinergic (parasympathetic) nervous system, preganglionic adrenergic (sympathetic) neurons, the neuromuscular junction in skeletal muscles, and multiple nerve endings in the central nervous system (Fig. 10-5). 

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