NMJ(Neuromuscular Junction )

Physiology Reference Book : Guyton

أحمد. صادق طه د

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Objectives• At the end of this lecture the student should be able to :• Describe the anterior horn cell and motor unit .• Describe and define the structure and function of the

neuromuscular junctuion .• Describe acetylcholine vesicles , exocytosis , EPP ( end-plate

potential ), acetylcholinesterase , drugs that inactivate cholinesterase( e.g., neostigmine ), Myasthenia Gravis .

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• Q:What is a Motor Unit ?

• الوحدة ؟ الحركية

• It is the motorneuron (AnteriorHorn Cell) and allthe muscle fibers it supplies

04/19/233 األمامي القرن عصبون هياآلمر ) العصبون ( يعنيال العضلية الخاليا كل و

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Neuromuscular Transmission

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The Neuromuscular junction consists ofA/ Axon Terminal : containsaround 300,000 vesicles whichcontain the neurotransmitteracetylcholine (ACh).B/ Synaptic Cleft :20 – 30 nm ( nanometer ) spacebetween the axon terminal & themuscle cell membrane. It containsthe enzyme cholinesterase whichcan destroy Ach .C/ Synaptic Gutter ( Synaptic

Trough)It is the muscle cell membranewhich is in contact with the nerve terminal . It has many folds called Subneural Clefts , which greatly increase the surface area , allowing for accomodation of large numbers of ACh receptors . ACh receptors are located here .

The entire structure of axon terminal , synaptic cleft and synaptic gutter is called “ Motor End-Plate ” .

ACh is synthesized locally in the cytoplasm of the nerve terminal , from active acetate (acetylcoenzyme A) and choline.

The enzyme responsible is Choline Acetyl Transferase . This enzyme is a marker of Cholinergic Neurons After being synthesized , ACh is rapidly absorbed into

the synaptic vesicles and stored there. The synaptic vesicles themselves are made in the nerve

soma (celol-body by Golgi apparatus ) . Then they are carried by Axoplasmic Transport to the

nerve terminal , which contains around 300,000 vesicles .

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• When a nerve impulsereaches the nerve terminal , it opens calciumchannels • calcium diffuses fromthe ECF into the axonterminal Ca++ releasesACh from vesicles bya process calledExocytosis . ACh combines with itsreceptors in the subneuralclefts. This opens sodium Na+ channels & Na+ diffusesinto the muscle causing alocal,non-propagatedpotential called the “ End-Plate Potential (EPP)”, whose value is 50 – 75 mV.

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This EPP triggers amuscle AP which spreadsinside the muscle to

makeit cntract• One nerve impulse canrelease 125 ACh

vesicles , which is more than

enoughto generate produce oneEnd-Plate Potential

(EPP) .

• After ACh acts on the receptors , it is destroyed (hydrolyzed) by the enzyme Acetylcholinesterase ( also called cholinesterase ) into Acetate & Choline . The Choline is actively reabsorbed into the nerve terminal to be used again to form ACh. This whole process of Ach release, action & destruction takes about 5-10 ms . 9 04/19/23

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Examples of Drugs Acting on the NMJ

Drugs that inactivate Cholinesterase , called Anticholinesterase drugs , preventing it from destroying

ACh& hence sparing ACh and allowing Ach to acccunulate &stimulate the muscle . Example of this drug category is Tensilon ( Edrophonium )

, which is used in to test for Myasthenia Gravis

•Thanks

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