The neuromuscular junction (NMJ) is a synaptic connection between the terminal end of a motor nerve and a muscle (skeletal/ smooth/ cardiac). It is the site for the transmission of action potential from nerve to the muscle. It is also a site for many diseases and a site of action for many pharmacological drugs.For convenience and understanding, the structure of NMJ can be divided into three main parts: a presynaptic part (nerve terminal), the postsynaptic part (motor endplate), and an area between the nerve terminal and motor endplate (synaptic cleft).
Nerve Terminal: A myelinated motor neuron, on reaching the target muscle, loses its myelin sheath to form a complex of 100-200 branching nerve endings. These nerve endings are called nerve terminals or terminal boutons. The nerve terminal membrane has areas of membrane thickening called active zones. Active zones have a family of SNAP proteins (syntaxins and synaptosomal-associated protein 25) and rows of voltage-gated calcium (Ca) channels. A nerve terminal also has potassium channels on its membrane and contains mitochondria, endoplasmic reticulum, and synaptic vesicles (SVs). Each SV stores around 5000-10000 molecules of acetylcholine (ACh), the neurotransmitter at NMJ. The SVs are concentrated around the active zone. The membrane of SVs has synaptotagmin and synaptobrevin proteins. These proteins are essential for fusion and docking of SVs at active zones. On arrival of an action potential at the nerve terminal, Ca channels open to cause influx. Increased Ca inside the nerve terminal causes a series of events leading to docking of SVs at active zones and exocytosis of the ACh from the synaptic vesicles into the synaptic cleft.[2][3][2][4]
Synaptic Cleft / Junctional Cleft: The space between the nerve terminal and the plasma membrane of muscle is called synaptic/junctional cleft and measures ∼50 nm. It is the site where presynaptic neurotransmitters, ACh is released before it interacts with nicotinic ACh receptors on the motor endplate. Synaptic cleft of NMJ contains acetylcholinesterase enzyme, responsible for the catabolism of released ACh so that its effect on the post-synaptic receptors is not prolonged.[2][3][2][4]
Motor End Plate forms theMotor End Plate forms the postsynaptic part of NMJ. It is the thickened portion of the muscle plasma membrane (sarcolemma) that is folded to form depressions called junctional folds. The terminal nerve endings do not penetrate the motor endplate but fit into the junctional folds. Junctional folds have nicotinic ACh receptors concentrated at the top. These receptors are ACh gated ion channels. Binding of ACh to these receptors opens the channels allowing the influx of sodium ions from the extracellular fluid into the muscle membrane. This creates endplate potential and generates and transmits AP to the muscle membrane.[2][3][4]
Mechanism
ACh is synthesized in the pre-synaptic terminal using choline and acetyl-CoA and the enzyme choline acetyltransferase. It subsequently goes through a series of modifications before being packaged in vesicles. Upon depolarization, an action potential travels down the axon, causing voltage-gated calcium channels to open, resulting in an influx of calcium ions into the nerve terminal. This causes the vesicles to migrate towards the nerve terminal membrane and fuse with the active zones.
Different vesicular (SNAP-25, syntaxin) and nerve terminal membrane proteins (synaptobrevin and synaptotagmin) play a role in the fusion of SVs to active zones and exocytosis of ACh into the synaptic cleft. The released ACh subsequently binds to nicotinic ACh receptors on the junctional folds of the motor endplate. The binding of ACh to receptors triggers the opening of ACh gated ion channels that allow the influx of sodium ions into the muscle. The sodium influx changes the postsynaptic membrane potential from -90 mV to -45 mV. This decrease in membrane potential is called endplate potential. In the NMJ, endplate potential is strong enough to propagate action potential over the surface of the skeletal muscle membrane that ultimately results in muscle contraction. To prevent sustained depolarization and muscle contraction, as well as to allow forNeurophysiological studies like supramaximal repetitive nerve stimulation (RNS) of the peripheral nerve at 3Hz and single #Animation #Animation #Animation #Animation ##Mosy watched #Easy #Easy ##All steps #Steps #Steos #Stepa#7 steps #Ali Zaman butt
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