NMJ (Neuromuscular Junction ) Physiology Reference Book : Guyton د. طه صادق أحمد

1. NMJ(Neuromuscular Junction ) Physiology Reference Book : Guytonد. طه صادق أحمد

2. 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 .

3. Q:What is a Motor Unit ? • الوحدة الحركية ؟ • It is the motor neuron (Anterior Horn Cell) and all the muscle fibers it supplies

4. Neuromuscular Transmission

5. The Neuromuscular junction consists of A/ Axon Terminal : contains around 300,000 vesicles which contain the neurotransmitter acetylcholine (ACh). B/ Synaptic Cleft : 20 – 30 nm ( nanometer ) space between the axon terminal & the muscle cell membrane. It contains the enzyme cholinesterase which can destroy Ach . C/ Synaptic Gutter ( Synaptic Trough) It is the muscle cell membrane which 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 .

6. 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 .

7. When a nerve impulse reaches the nerve terminal , it opens calcium channels  calcium diffuses from the ECF into the axon terminal  Ca++ releases ACh from vesicles by a process called Exocytosis . ACh combines with its receptors in the subneural clefts. This opens sodium Na+ channels  & Na+ diffuses into the muscle causing a local,non-propagated potential called the “ End-Plate Potential (EPP)”, whose value is 50 – 75 mV.

8. This EPP triggers a muscle AP which spreads inside the muscle to make it cntract One nerve impulse can release 125 ACh vesicles , which is more than enough to generate produce one End-Plate Potential (EPP) .

9. 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 .

11. 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

12. Thanks