Neuromuscular Junction Lecture Notes PDF

‫بسم الله الرحمن‬ ‫الرحيم‬ NEUROMUSCULAR JUNCTION Dr.Mohammed Sharique Ahmed Quadri Dr Nisreen Daffa Alla Omer M.B.B.S, Ph. D (Human Physiology), MSc medical education Assistant prof. Physiology Al Maarefa University& University o...

‫بسم الله الرحمن‬ ‫الرحيم‬ NEUROMUSCULAR JUNCTION Dr.Mohammed Sharique Ahmed Quadri Dr Nisreen Daffa Alla Omer M.B.B.S, Ph. D (Human Physiology), MSc medical education Assistant prof. Physiology Al Maarefa University& University of Khartoum  Neuromuscular junction (example of chemical synapse) Neuromuscular junction : the synapse between somatic motor neuron and muscle fiber is called the neuromuscular junction Somatic Motor neurons : are the nerves that innervate muscle fibers Motor unit : single motor neuron and the muscle fibers it innervate 2  Sequence Of Events At Neuromuscular Junction Action potential Ca2+ Presynaptic terminal Voltage-gated Ca2+ channel 1)Action potentials arriving at the presynaptic terminal cause voltage-gated Ca2+ channels to 3  Sequence Of Events At Neuromuscular Junction (continued) Ca2+ Synaptic vesicle Acetylcholine 2)Ca2+ uptake into the terminal causes release of the Ca2+ diffuse into theacetylcholine neurotransmitter cell and cause synaptic vesicles into synaptic to release cleft , which acetylcholine, has a neurotransmitter been synthesized molecule. and stored into synaptic vesicles4  Sequence Of Events At Neuromuscular Junction (continued) Ca2+ Presynaptic terminal Synaptic cleft Acetylcholine 3)Ach travels across the synaptic cleft to postsynaptic membrane Acetylcholine which diffusesisfrom also theknown as motor presynaptic end terminal plate. across the 5  Sequence Of Events At Neuromuscular Junction (continued) 4)Motor end plate contains Action potential nicotinic receptors for Ach , Ca2+ which are ligand gated ion 1 Synaptic Presynaptic terminal channels Voltage-gated Ca2+ channel vesicle 2 Synaptic cleft 5)Ach binds to the alpha 3 subunits of nicotinic Acetylcholine Postsynaptic membrane receptors and causes Na+ Acetylcholine bound to receptor site opens conformational change. ligand-gated Na+ channel 44 6)When conformational changes occurs ,the central core of channels opens & Na+ Acetylcholine bound to receptor site opens permeability of motor end ligand-gated Na+ channel 6 plate to Na+ & K+ increases Acetylcholine molecules combine with their receptor sites and cause ligand-gated Na+ channels to open.  End plate potential 7)When the ion channel on post synaptic membrane opens both Na+ & K+ flow down their concentration gradient. 8)when Ach triggers opening of these channels more Na+ moves inwards than K+ out wards, depolarizing the end plate. This potential change is called end plate potential (EPP). 9) End plate potential EPP is simply 7 Acetyl cholinesterase ends Ach activity at N.M junction To ensure purposeful movement ,muscle cell electrical response is turned off by acetylcholinestrase(AchE), which degrade Ach to choline & acetate About 50%of choline is returned to the presynaptic terminal by Na+choline transport to be reused for Ach synthesis. Now muscle fiber can relax ,if sustained contraction is needed for the desired movement another motor neuron AP leads to release of more Ach 8  Agents &disease that alters the function of N.M junction  Black widow spider venom the venom of black widow spider exerts its effect by triggering explosive release of Ach from the storage vesicles, not only at N.M junction but all cholinergic sites. all cholinergic sites undergoes prolong depolarization. The most harmful result is respiratory failure 10  Botulinum toxin Botulinum toxin: botulinum toxin exerts its lethal effect by blocking the release of Ach. Clostridium botulinum poisoning most frequently result from improperly canned food contaminated with clostridia bacteria Death is due to respiratory failure caused by inability to contract diaphragm. 11  Curare curare competitively binds to Ach receptor sites on motor end plate ,so Ach can not combine with these sites to open ion channels.and muscles paralysis ensues. In sever poisoning person dies of respiratory failure In past it was used as deadly arrowhead poison. 12  Myasthenia gravis A disease involving N.M junction is characterized by the extreme muscular weakness (myasthenia=muscular & gravis=severe) It is an auto immune condition (auto immune means immunity against self) in which the body erroneously produces antibodies against its own motor end plate ach receptors. Thus not all Ach molecules can find functioning receptors site with which to bind. As a results ,AchE destroys much of Ach before it ever has a chance to interact with receptor site & contribute to EPP. 13 14 Identify the labelled structures Identify the labelled structures  References Human physiology by Lauralee Sherwood, fifth edition Text book physiology by Guyton &Hall,11th edition Text book of physiology by Linda.s contanzo,third edition 17