Neuromuscularjunctionnervemusclephysiology.pptx

Important topic

1. Neuro- m u s cu l a r junction

2. To draw the schematic diagram of Neuro - muscular junction To describe the events of Neuromuscular transmission Classify neuromuscular blockers & give mechanism of action D isorders of neuromuscular junction Learning objectives

3. Neuro-muscular junction/ Myoneural junction Junction between Motor neuron & Muscle fibre Action potential from nerve is transmitted to muscle through this junction Introduction

4. Physiological anatomy of NMJ Presynaptic membrane (terminal buttons) : small, clear vesicles containing acetylcholine SYNAPTIC CLEFT/SPACE : space between pre and post-synaptic membrane, 20-40 nm, also contain enzyme ACETYLCHOLINESTERASE Postsynaptic membrane (motor end plate): thickened portion of muscle membrane at the junction

5. Neuron innervating skeletal muscle fibre – Motor Neurons Near muscle fibre it looses its myelin sheath & divides into axon terminals Each terminal is expanded at its tip to form Synaptic Knob / Terminal Button ) Presynaptic portion- Axon terminal

6. The motor neuron its axon, its terminal with muscle fibre it supplies – form MOTOR UNIT Terminal button lies in a groove- Synaptic Trough Vesicles gather at specific points – Active Zones – Membrane at active zone modified to form Dense Bars – contains numerous voltage gated Ca channels Presynaptic portion- Axon terminal

7. 50-100 nm wide Filled with extracellular fluid C ontains acetyl- choline-esterase It hydrolyses Ach into Acet ic acid & Choline Synaptic cleft

8. It’s a part of sarcolemma S everal folds Junctional Folds increases membrane surface area Contains Ach-receptors voltage gated Na channels Post synaptic membrane

9. Nicotinic type 15-40 millions /end plate Chemically gated ion channels Contains voltage gated Na channels & allow passage of only Cations Acetylcholine receptors

10. Def – Transmission of impulses from motor neuron to skeletal muscle fibre. Mechanism 3 parts Presynaptic events Synaptic events Post synaptic events. Neuromuscular transmission

11. Main Purpose – To release acetyl choline into synaptic cleft Steps – Action potential arrive at axon terminal & Depolarize membrane of terminal button Activate & open voltage gated Ca channels -Ca influx – increases movements of Microtubules & Microfilamants- causes migration of Neurotransmitter vesicles to pre-synaptic membrane - DOCKING Release acetylcholine into cleft by Exocytosis Presynaptic events

12. Quantal Release One vesicle of acetyl choline – Quanta Process of release of 1 vesicle is Quantal Release Sir Katz, Euler & Axelrod received Nobel prize in 1970 for Quantal release phenomenon Presynaptic movements

13. Binding of acetylcholine to receptors at post synaptic membrane On the way some are hydrolyzed by A ChE & remaining act on receptors Events at synaptic cleft

14.      Generate Action Potential in sarcolemma A C h diffuses into cleft & bind with post- synaptic ACh receptors ACh Gated Ion Channels 5 sub uints When 2 molecules are attached conformational change occurs in tubular channels & open it & increases Na influx Post synaptic membrane events

15. RMP of postsynaptic membrane is -80 to -90 mV Influx of Na channels causes local positive potential change – END PLATE POTENTIAL It’s localized, Non-Propogated, Does not obey All or None Law But when critical level of -60mv reached triggers action potential in muscle fibre in both direction End plate potential

16. EPP Only 6 vesicles are required for activation from -90 to -65mv Each nerve impulse releases 60-125 Ach vesicles Every vesicle has 10,000 molecules of Ach 10 fold safety factor Action potential is always generated

17. At rest, small quantity of acetyl choline are released from nerve terminal Each vesicle release produces weak end plate potential about 0.5mv – Miniature End Plate Potential Miniature end plate potential

18. Within 1 ms by 2 ways Mostly destroyed by A ch - estarase in synaptic cleft Remaining Diffuses Out of synaptic space & no longer available for action Reuptake by exchanger - Reused Removal by ACh esterase

19. Myasthenia Gravis Auto Immune disease Anti bodies are produced against Acetylcholine Receptors & destroy these channels Disorders of NMJ

20. So acetyl choline released will not produce adequate end plate potential & excite muscle fibre So patient dies of paralysis of Respiratory Muscles Myasthenia gravis

21. Treatment Ameliorated for several hours by administering neostigmine Anticholinesterase drug Larger than normal amounts of ACh accumulate in the synaptic space Within minutes, some of these paralyzed people can begin to function almost normally

22. L am b e r t - E a t o n S yndrome Anti bodies are produced against calcium channels present on pre-synaptic membrane Ca influx decrease & decreases release of acetyl choline Disorders of NMJ

23. Myasthenia gravis LEMS Antibodies against receptor for ACh on postsynaptic membrane Antibodies against presynaptic Ca channels Pr i m a r i l y attacks the ocular & bulbar muscles Starts at extremities Weakness worsens with activity Weakness improves with activity Associated with tumours of thymus Associated with Ca lung Tt = neostigmine ( ACh esterase inhibitor) Tt = Aminopyriridines

24. What is the rationale behind the use of C alabar bean as a lie detector by some native tribes of West Africa? Calabar bean - physostigmine , an AChE inhibitor innocent - consumes rapidly local gastric irritation (possibly due to accumulation of ACh at parasympathetic postganglionic nerve endings in the stomach) vomits guilty - scared & apprehensive , small sips suffers less gastric irritation, does not vomit, in intestines gets absorbed

25. Drugs affecting NMJ STIMULAT E T HE MUSCLE F I BER BY ACh LIKE ACTION methacholine , carbachol and nicotine not destroyed or are destroyed very slowly by cholinesterase STIMULATE THE NEURO-MUSCULAR JUNCTION BY INACTIVATING ACETYL- CHOLINESTERASE neostigmine, physostigmine diisopropyl flourophosphate : inactivate acetylcholinesterase for weeks, “nerve” gas poison BLOCK TRANSMISSION AT NEURO MUSCULAR JUNCTION Curariform drugs d- Tubocurarine Used in surgery because they relax muscle and abolish reflexes

26. Drugs affecting NMJ

27. Summary