This is an extract of our Essay On Neuromuscular Transmission document, which we sell as part of our Physiology and Pharmacology Notes collection written by the top tier of Oxford students.
The following is a more accessble plain text extract of the PDF sample above, taken from our Physiology and Pharmacology Notes. Due to the challenges of extracting text from PDFs, it will have odd formatting:
Neuromuscular transmission Neuromuscular junctions play a vital role in transmitting action potentials from the motor neurone to the muscle fibres (e.g. skeletal muscle fibres). Structurally, motor neurons have long axons which divide into many branches known as axon terminals and each axon terminal makes contact with an individual muscle fibre. All the muscle fibres activated by the branches that divide from one axon from one motor neuron is collectively known as the motor unit. The neuromuscular junction is defined as the interface between the branch of the axon and the muscle fibre it is in contact with. There are three key structures that make up the neuromuscular junction. One is the bulbous shaped endings of the axon terminal, which is known as the bouton and the membrane of the bouton is commonly referred to as the presynaptic membrane. Electron micrographs of the bouton reveal that there are many spherical synaptic vesicles contained within them. The second is the post synaptic membrane of the muscle fibre that lies directly under the axon terminal and this membrane has many invaginations which make up the post-junctional folds. The third structure is the synaptic cleft, which is the gap between the pre and post synaptic membranes, and it contains meshwork of proteins and proteoglycans. It also contains a high concentration of the enzyme acetylcholinesterase which is the enzyme that breaks down the neurotransmitter acetylcholine. The neuromuscular junction is described as a chemical synapse because the electrical signal (action potential) is converted into a chemical signal (diffusion of neurotransmitters) and then regenerated into an electrical signal. The key steps that are involved in chemical synapses like the neuromuscular junction are the following; release of the transmitter from the synaptic vesicles into the synaptic cleft, diffusion of the transmitter across the synaptic cleft, activation of the post synaptic membrane by the binding of transmitter molecules to the receptor protein on the post synaptic membrane and consequently an action potential being generated in the muscle cell. The evidence that shows that neuromuscular junctions are chemical synapses comes from the fact that when the motor nerve is excited there is a transient depolarisation in the muscle after a delay of a few milliseconds. It is the delay that signifies that the junction is a chemical synapse rather than an electrical synapse. The first stage of neuromuscular transmission is that the neurotransmitter is packaged into synaptic vesicles. The synaptic vesicles are synthesised in the cell body of the motor neurone by the RER, followed by the Golgi Apparatus. The empty vesicle is then transported through the axon by a microtubule system to the nerve terminal. The neurotransmitter acetylcholine is synthesised when choline and acetyl CoA react together and this reaction is catalysed by the enzyme choline acetyltransferase. When the vesicle reaches the nerve terminal the non peptide neurotransmitter, acetylcholine, moves into the vesicle through the acetylcholineproton exchanger by secondary active transport. The efflux of protons down the concentration gradient is coupled with the uptake of acetylcholine. The
concentration gradient for the hydrogen ions is maintained by the proton pump which uses the hydrolysis of ATP to actively transport hydrogen ions into the vesicle. Once each synaptic vesicle is filled with 6000 to 10000 molecules of acetyl choline, the vesicles are docked in the active zones of the presynaptic membrane. The next stage of neuromuscular transmission is the depolarisation of the presynaptic membrane. This occurs when an action potential reaches the axon terminal. If the depolarisation of the membrane leads to a membrane potential that is greater than the threshold value for voltage gated calcium ion channels, it leads to the opening of these channels found in the active site. This results in an influx of calcium ions into the presynaptic membrane. The influx of Calcium ions is vital as it triggers the excocytotic fusion of synaptic vesicles containing acetyl choline with the presynaptic membrane. This occurs because calcium ions bind to the synaptotagmin which is an intergral membrane protein found in synaptic vesicles and as a result it triggers fusion. Experiments using a specific type of voltage gated calcium ion channels, the N type isoform, have shown that it is the calcium ions that trigger the fusion of the synaptic vesicles. When w-conotoxin, which is a peptide toxin, is exposed to the frog nerve muscle there is no influx of calcium ions into the presynaptic membrane even when the membrane is depolarised. This occurs because the toxin blocks the N type calcium channels. Consequently the release of neurotransmitter into the synaptic cleft is inhibited. There are series of stages that are involved with the fusion of synaptic vesicles. Firstly the synaptic vesicles which contain the proteins, synaptotagmin and synaptobrevin within the plasma membrane move towards the axon terminal membrane. The membrane of the axon terminal contains proteins syntaxin and SNAP-25. The next stage is the dissociation of n-Sec-1 which forms a cap over the syntaxin protein. This liberates syntaxin which then winds around SNAP 25 to form a complex. The membrane protein synaptobrevin found in the synaptic vesicle then coils around the syntaxin/SNAP-25 complex and forms a ternary complex. The three proteins continue to wind around each other and form a tight bundle of alpha helices. This action draws the synaptic vesicle towards the presynaptic membrane. In the bacterial infection caused by 'clostridium botulinum' the toxin botulinum is released. This toxin cleaves to the three proteins that form the ternary structure and as a result prevent the fusion of the synaptic vesicles. Due to this the neurotransmitter is not released into the synaptic cleft. However these neurotoxins have a medical use. The botulinum toxin is used to treat muscle spasms and also found in Botox which is a temporary treatment for facial wrinkles. Following the movement of the synaptic vesicles towards the presynaptic membrane, the influx of calcium ions and its binding to synaptotagmin triggers the excocytotic fusion of the vesicle. This releases the neurotransmitter acetylcholine which diffuses across the synaptic cleft. The empty synaptic vesicle is then taken back up into the axon terminal by endocytosis. This occurs when a soluable a-SNAP protein binds to the ternary complex. This promotes the binding of an ATPase enzyme which uses the
Buy the full version of these notes or essay plans and more in our Physiology and Pharmacology Notes.