Neuromuscular Junction Notes

Neuromuscular junction

-if asked to talk about NMJ in essay- always start by describing the organisation of the synapse

-site of information transfer from a motor neuron to a muscle cell

-chemical synapse- SYNAPSE- specialised structure where information transfer takes place without physical interactions between 2 participating cells. CHEMICAL SYNAPSE- an electrical signal, an action potential is turned into a chemical signal, neurotransmitters that diffuses from the presynaptic neuron into the post synaptic neuron where it binds to receptors and converts the chemical signal back into an electric signal of an action potential

-evidence that is a chemical synapse- delay between the action potential in the muscle cell and the action potential in the presynaptic axon terminal

which has a calcium dependent neurotransmitter release, quantal release of NT

-cholinergic transmission: motor nerves supplying skeletal muscle

morphology and function of NMJ

-motor unit: whole assembly of muscle fibres that are innervated by the axon of one motor neuron

-the axon subdivides into many branches known as the axon terminals- unmyelinated nerve processes, bulbous shaped ending- boutons- and each of these make a single point of contact with a skeletal muscle fibre, midway along the length of the muscle fibre. The post synaptic membrane of the muscle fibre is directly under the axon terminal and has extensive invaginations- post junctional folds. The gap between the axon nerminal and the post synaptic membrane is known as the synaptic cleft- 50nm wide and is filled with a meshwork of proteins and proteoglycans

Steps involved in a neuromuscular transmission

1. Synthesis of neurotransmitter occurs in the presynaptic membrane

Cholinergic transmission: the neurotransmitter, acetylcholine is synthesised in the presynaptic membrane outside of the vesicle using choline and acetyl CoA and the enzyme choline acetyl transferase

-nerves can’t make enough choline, choline is taken up from blood, comes from diet and liver

-the Ach is then transported into vesicles, formed from the cell bodies of the motor neurones that are then transported to the axon terminal by microtubules, by ACH-H exchange protein. The carrier protein couples the influx of Ach, with the efflux of H and is an example of secondary active transport. The protons move down the electrochemical gradient which is form by the proton pump powered by the ATP

-vesamicol- drug that inhibits this carrier protein and prevents the uptake of ACH into vesicles

Evidence that the neurotransmitter is stored in vesicles

-electron microscope shows clear vesicles – Key evidence: must mention this in essay in conjuction with MEPP

-the evidence that NT are stored in vesicle is shown by the quantal release

-when a microelectrode is placed in the end plate of a frog muscle fibre to measure the resting membrane potential- found that there were depolarisation of O.4 mv at random intervals. These depolarisations known as miniature end plate potentials- size of these miniature end plate potentials showed that potential were discrete multiples of unitary amplitude. 1 quantum- corresponding to the release of ACH from one synaptic vesicle

-the miniature end plate potentials are purely spontaneous release (basal release), keeps th receptors positioned in the right place beneath the presynaptic terminal

-when the end plate potential is measured, the potential is of integer multiples of the miniature end plates- quantal nature

2) action potential in the presynaptic membrane

When an action potential arrives in the presynaptic membrane it depolarises and stimulates the opening of voltage gated calcium ions.

-the voltage gated calcium channels are held near the active zone where the vesicles are docked and primed by the t snare protein syntaxin- this ensures that there is a high calcium concentration locally, this increases the speed and there is a minimal delay in calcium binding to the vesicles

The influx of calcium ion down the electrochemical gradient stimulates the release of vesicles

-evidence that Ca- plays an essential role in NMJ

-end plate potential potential increase when the external concentration of Ca increased- to show that calcium ions are involved in the presynaptic neurone and not the post synaptic neuron- injection of calcium ions

Role of calcium and the t snare and v snare proteins

-vesicles that are packed with ACH, have two important V-snare proteins that are involved in the exocytosis

-synaptotagmin and synaptobrevin

-the presynaptic membrane of the axon has T-snare proteins- syntaxin and SNAP-25

-SYNTAXIN has a cap called n-sec 1- when this dissociates it winds around SNAP 25- this complex forms a ternary complex with synaptobrevin.

-as the 3 SNARE proteins wind around each other to form a tighter alpha helices- it draws the vesicles closer and brings the vesicles and membrane into tight apposition

-the entry of calcium ions bind to synaptotagmin and triggers the fusion of the vesicle...

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