Synaptic Transmission & Neuromuscular Junction PDF

SYNAPTIC TRANSMISSION & NEURO-MASCULAR JUNCTION OBJECTIVES Synapse and synaptic transmission Describe the structure of neuromuscular junction Understand the mechanism by which neuromuscular transmission occur Understand the pathophysiology of the neuromuscular disorders. Know the drugs a...

SYNAPTIC TRANSMISSION & NEURO-MASCULAR JUNCTION OBJECTIVES Synapse and synaptic transmission Describe the structure of neuromuscular junction Understand the mechanism by which neuromuscular transmission occur Understand the pathophysiology of the neuromuscular disorders. Know the drugs acting on the neuromuscular junction  SYNAPSE Synapses:- are specialized junctions through which NS cells signal to one another and to effectors (muscles or glands). They provide the means through which the NS connects to and controls the other systems of the body. Types Synapses – types of connections (a)-Axodendritic (b) Axosomatic (c) Axoaxonic  SYNAPES Synapse : -specialized junction where an axon terminal contacts another neuron or other cell type  Types of synapses A. Electrical synapses B. Chemical synapses  An understanding of synaptic transmission is necessary to understand the operations of the nervous system (ie. actions of psychoactive drugs, causes of mental disorders, neural basis of learning and memory)  A-Electrical Synapses  Allows the direct transfer of ionic current from one cell to the next.  Gap Junction is composed of 6 connexins that make up a connexon. (Pore size = 2nm)  Ions can flow bidirectionally.  Cells are electronically coupled.  Conduction speed is very fast. B. CHEMICAL SYNAPSE  B- CHEMICAL SYNAPSES  Synaptic cleft 20 – 50 nm wide Held together by a fibrous extracellular matrix  Synaptic knoub (presynaptic element) Contains synaptic vesicles (~50nm in diameter) and secretory granules (~100 nm) called large, dense core vesicles.  Membrane differentiations – accumulations of proteins on either side of the synaptic cleft Active zones – presynaptic site of neurotransmitter release Postsynaptic density – contains receptors to translate intercellular signal (neurotranmitter) into an intracellular signal (chemical change or membrane potential change)  Synaptic Transmission What makes impulses move in one direction ?  MECHANISM OF SYNAPTIC TRANSMISSION Synaptic transmission begins when an AP propagates from the main axon into the end feet  DP of the feet open voltage gated calcium channels leading to calcium influx  Calcium bind to specific proteins that cause fusion of vesicles with plasma membrane and exocytosis of Ach.  Ach cross the cleft and bind to nicotinic receptors in the junctional fold causes opening of the voltage gated sodium channels causing Na+ influx  Increasing Na+ influx resulting in DP of the muscle which is called end plate potential  EPP normally reaching the firing level, which start AP along the surface of the muscle  Ach is rapidly hydrolyzed by choline esterase enzyme, so that re-excitation of the muscle would not occur  If the Ach released does not destroyed ???  Ach will accumulate >> Na+ channels remain continuously open >>continuous DP (called DP block) >>strong muscle contraction flowed by paralysis. Organo phosphorous compounds destroys Ach esterase permanently causing muscle paralysis and death PROPERTIES OF SYNAPTIC TRANSMISSION 1. Synaptic delay 2. Synaptic fatigue. 3. Effect of PH 4. Effect of chemical and Drugs. 5. Convergence and divergence 6. Facilitation 7. inhibition 8. summation A. temporal B. spatial Motor end plate  Events during N-M Transmission Action potential in Presynaptic Motor axon terminal Increase in Ca++ ion permeability and influx of Ca++ into the Axon Terminal Release of Ach from the Synaptic Vesicles into the Synaptic Cleft Diffusion of Ach to Postjunctional membrane  Events during N-M Transmission Combination of Ach with specific receptors on postjunctional membrane Increase in permeability of postjunctional membrane to Na++ and K+ causes EPP Depolarization of areas of Muscle membrane adjacent to end plate and initiation of AP  Factors affecting NM Transmission 1. Ions 2. Drugs – curare, antibiotics 3. Acid – base conditions 4. Temperature  STRUCTURE OF NMJ  What is Neuromuscular junction?  A neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of a motor neuron with the skeletal muscle.  STRUCTURE OF NMJ The axon supplying a skeletal muscle fiber, loses its myelin sheath and divides into terminal buttons(end feet). End feet contains small vesicles that contains Acetylcholine. The endings fit into depression in motor end plate (the thick portion of muscle membrane) or junctional folds Ach is synthesized in the end feet (neuronal ending) from choline & acetyl- coenzyme A by choline acetyltransferase enzyme. The junctional fold contain nicotinic receptors for Ach, which is the ligand- gated channels The sarcoplasm at the motor end plate is granular and contain cholinesterase enzyme Neuromuscular disorders Myasthenia gravis  An autoimmune disease  Autoantibodies formed against Ach receptors, bind with theses receptors and destroyed it.  So that there is no formation of AP and no muscle contraction.  These patients are characterized by : weakness and fatigue.  Muscle weakness increase with repetitive muscles  Weakness partially recover with rest.  Treated by AchE inhibitor (neostigmine) which decrease degradation of Ach. Patient of myasthenia usually presnted with drooping of both the eyelids  DRUGS ACTING ON THE NEUROMUSCULAR JUNCTION (1) Drugs that block the release of Ach from the nerve endings (e.g.Botulinum toxin) (2) Drugs that destroys the Ach E enzyme : e.g. Neostigmine & physostigmine These destroy the AchE, so that the availability of Ach in the synaptic cleft is prolonged which increase the number of AP leading to repetitive muscle stimulation and muscle spasm Which can cause a death due to laryngeal spasm (3) Drugs that bind with Ach receptors and block the action of Ach : e.g. Curare This drug block the Ach receptor, so that Ach will not bind with the receptors, which prevent formation of action potential in the muscle , the muscle can not contract and become paralyzed I hope you didn´t