Neuromuscular junction cholinergic nerve ending

The neuromuscular junction has a cholinergic nerve ending and so is activated by anticholinesterases which allow acetylcholine to persist, causing muscle fasciculation. Prolonged activation leads to a secondary depolarising neuromuscular block. 

Botulinum toxin is one of several toxins produced by the bacterium Clostridium botulinum. The toxin binds with high affinity to peripheral cholinergic nerve endings, such as those at the neuromuscular junction and in the autonomic nervous system, preventing the release of the neurotransmitter acetylcholine (1). This action at the neuromuscular junction can cause weakness and even paralysis of the muscles supplied by the affected nerves. Sprouting of the terminal nerves eventually results in re-innervation of the muscles and return of function. Doses are measured in mouse units (MU), IMU being the LD50 in Swiss-Webster mice. 

Acetylcholine is a neurotransmitter at the neuromuscular junction in autonomic ganglia and at postgangHonic parasympathetic nerve endings (see Neuroregulators). In the CNS, the motor-neuron collaterals to the Renshaw cells are cholinergic (43). In the rat brain, acetylcholine occurs in high concentrations in the interpeduncular and caudate nuclei (44). The LD q (subcutaneous) of the chloride in rats is 250 mg/kg. 

Acetylcholine and agents acting at the autonomic ganglia or the neuromuscular junctions interact with nicotinic cholinergic receptors to initiate the end plate potential in muscle or an excitatory postsynaptical potential in nerve. The nicotinic receptor in skeletal muscle is a pentamer composed of four distinct subunits. 

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). 

C. Botulinum toxins cannot penetrate intact skin but can be absorbed through wounds or across mucosal surfaces. Once absorbed, the toxins are carried to presynaptic nerve endings at neuromuscular junctions and cholinergic synapses where they bind irreversibly, impairing the release of acetylcholine. 

Calcium is indispensable for the release of transmitter by the nerve endings. This has been shown for cholinergic neurons in the neuromuscular junction, in autonomic ganglia and in the cerebral cortex as well as for the adrenergic sympathetic nerves and for some neurons releasing an unidentified transmitter in squid... 

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