Neuromuscular junction and Neuromuscular transmission

Structure of the neuromuscular junction and events occurring at the neuromuscular junction.

1. GOOD AFTERNOON EVERYONE!

2. Facilitator: Shailesh Adhikari Presented by group “C” Bhawana Kafle Bibek Bhandari Bijaya Pun Chandan Kumar Sah Deekshya Devkota Dilip Kumar Thakur Duman Thapa Gyanendra Bakhati Gyanendra Suyal Sujan Tamang

3. Learning objective -structure of neuromuscular junction -series of events occurring at neuromuscular junction

4. WHAT IS NEUROMUSCULAR JUNCTION? It is the junction between terminal of motor neuron and muscle fiber.

5. Structures of axon terminal: Presynaptic membrane Mitochondria Synaptic vesicles Sodium choline co-transporter Microfilaments and tubules Voltage gated calcium channels

6. Structures of synaptic cleft: - basal lamina (organized layer of extracellular matrix inside the synaptic cleft) -Acetyl cholinesterase enzyme This Photo by Unknown Author is licensed under CC BY-SA-NC

7. Structures of postsynaptic membrane: Synaptic trough or gutter - motor endplate invaginates inside the muscle fiber and form depression subneural cleft: numerous folds of post synaptic membrane -nicotinic acetylcholine receptors - ligand gated ion channels

8. Neuromuscular transmission Transfer of information from motor nerve endings to the muscle fiber through neuromuscular junction to initiate muscle contraction .

9. Events in neuromuscular transmission : 1. Propagation of action potential to the axon terminal 2.Opening of voltage gated calcium channels in the membrane of axon terminal Influx of calcium ions from ECF to the axon terminal Migration and attachment of acetylcholine vesicles to the presynaptic membrane 3.Release of acetylcholine via exocytosis Acetylcholine diffuses into synaptic cleft

10. 4. Action of acetylcholine binds with nicotinic Ach receptor in the post synaptic membrane Formation of Ach receptor complex opening ligand gated sodium channels Sodium from ECF diffuses into muscle fiber End plate potential develops

11. 5. Development of end plate potential(EPP) RMP at muscle fiber is -90mv Sudden influx of Na+ into the muscle fiber when the Ach gated ion channels open causes electrical potential inside the fiber at the local area of the end plate to increase in the positive direction as much as 50 to 75mv creating a local potential called endplate potential . EPP is a graded potential(non-propagative, short distance signal) EPP initiates an action potential that spreads along the muscle membrane and thus causes muscle contraction.

12. 5. Destruction of acetylcholine Rapidly removed by two means: 1) destroyed by enzyme acetylcholinesterase 2)small amount of acetylcholine(Ach) diffuses out of synaptic space Ach in synaptic cleft is destroyed very quickly, within 1millisec by enzyme Ach esterase. Ach is so potent that even this short duration is sufficient to excite the muscle fiber. Rapid destruction of acetylcholine prevents the repeated excitation of muscle fiber and allows muscles to relax.

13. Reuptake process -Ach esterase splits Ach into inactive choline and acetate. Acetylcholine Ach esterase acetate+ choline -Choline is taken back into axon terminal from synaptic cleft by nerve ending via sodium choline co-transport and reused for synthesis of acetylcholine -acetate diffuses into ECF choline + acetate ATP acetylcholine

14. Miniature end plate potential Small quanta of Ach released at resting condition which in turn generate small potential difference about 0.5mv When a nerve impulse reaches the ending the number of quanta released by several order of magnitude that result in large endplate potential that exceeds the firing level of muscle fiber .

15. Neuromuscular blockers Drugs which prevent transmission of impulse across neuromuscular junction by blocking Ach receptors. Eg : curare , bungarotoxin(from snake venom),botulinum toxin Useful in surgical and trauma care to restrict muscle contraction.

16. Neuromuscular stimulators Drugs stimulating neuromuscular transmission Mechanism: Inactivates Ach esterase Repeated stimulation from acetylcholine Continuous contraction of muscle fiber use: treating weak or paralyzed muscle Example : Neostigmine, Physostigmine

17. Applied physiology Myasthenia gravis Autoantibodies against acetylcholine receptors. Blockade of acetylcholine receptors.

18. References: GUYTON AND HALL : Textbook of Medical Physiology(13 th edition pg.89) GANONG’S Review of Medical Physiology(23 rd edition 2010, page number:115) K Sembulingam : Essentials of MEDICAL PHYSIOLOGY(6 th edition 2013, page number:200) https://www.khanacademy.org/ https://www.ncbi.nlm.nih.gov/ https://www.wikipedia.org/

19. Presented by Bhawana Kafle Bibek Bhandari Bijaya Pun Chandan Kumar Sah Deekshya Devkota Dilip Kumar Thakur Duman Thapa Gyanendra Bakhati Gyanendra Suyal Sujan Tamang Thank you!