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Colden - Neuromuscular Junctio
Neuromuscular Junction
17
Physiology
08/14/2008

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Term
What are the basics of the neuromuscular junction?
Definition
It is the synapse between a motorneuron and a muscle fiber

also known as a motor-end plate

Acetylcholine is the NT used

The receptors are nicotinic
Term
What is the importance of the membrane in-folding at the plate?
Definition
The in-folding provides more membrane space which allows there to be more nicotnic ACh receptors

The in-folding also causes ACh to stay in the junction longer, prolonging its effect
Term
What are the main steps in neuromuscular transmission?
Definition
1) action potential in the presynaptic neuron opens up voltage-gated Ca2+ channels

2) Ca2+ flows into the cell down its gradient and causes

3) exocytosis of acetyl choline

4) two molecules of acetylcholine bind to the nicotinic receptor on the postsynaptic neuron

5) the non-specific ligand-gated ion channel opens up and Na+ flows in and K+ flows out

6) depolarization of the motor end plate leads to an action potential in the muscle cell

7) ACh is broken down by AChesterase

8) Choline uptake occurs through the Na+-choline cotransporter

Term
How does re-uptake differ for ACh compared to biogenic amines
Definition
ACh is broken down into its metabolites choline and acetly CoA before re-uptake.

Biogenic amines like NE and EPI can be re-uptook directly
Term
What is a miniature end plate potential (MEPP)?
Definition
An end plate potential (EPP) is the depolarization of the motor end plate which causes an action potential

a MEPP is an EPP where the depolarization isn't strong enough to reach threshold and cause an action potential

this can be caused by 1 vesicle of ACh molecules binding spontaneously (not part of purposeful transmission) to receptors

also can occur in the presence of the drug curare which competes with ACh for the nicotinic receptors
Term
What are the main characteristics of an end plate potential?
Definition
It is the potential that occurs at the motor end plate that causes an action potential

It is always superthreshold. Usually it is significantly more than what is needed to reach threshold

Term
What is the structure of the ACh (nicotinic) receptor?
Definition
It is a nonselective ligand-gated ion channel

It is composed of five subunits

Requires the binding of two ACh molecules to open the channel
Term
Explain how the nonselective ion channel works to cause depolarization in the motor end plate
Definition
The channel allows cations to flow in and out. Na+ flows in, K+ flows out, and Ca2+ can flow in (not significant)

The inward driving force of Na+ is much higher than the outward driving force of K+. This is because RMP (-60 mV) is a lot closer to EK (-75 mV) than ENa (+60 mv).

The electrical driving force for Na+ overcomes the stronger chemical gradient for K+

This results in more Na+ flowing in than K+ flowing out and causing a depolarization.
Term
What is the affect of TTX on the neuromuscular junction?
Definition
It can block both the nerve action potential and the muscle action potential because it prevents voltage-gated Na+ channels from opening.

Saxitoxin can have similar effects
Term
How can calcium and magnesium levels affect the neuromuscular junction?
Definition
Low ECF levels of Ca2+ decreases Ca2+ influx at the presynaptic neuron and decreases ACh release

High ECF levels of Mg2+ have a similar effect because Mg2+ can go through the voltage-gated Ca2+ channels
Term
What is the affect of botulinum toxin on the neuromusclar junction?
Definition
It blocks the release of ACh from the presynaptic terminal causing total blockade of NM transmission
Term
What is the effect of curare on the neuromuscular junction?
Definition
Curare competitively binds to the ACh receptor

It inhibits end plate potentials from forming
Term
What is the effect of physostigmine and other
anticholinergics (neostigmine) on the neuromuscular junctions?
Definition
These compounds block the hydrolysis of ACh by AChesterase.

This increases the level of ACh and increases NM transmisson
Term
What is the effect of metacholine and nicotine on the neuromuscular junction?
Definition
These are agonists which can reproduce the affect of the ACh.

They increase NM transmission by increasing end plate potentials
Term
What is the effect of hemicholinium on the neuromuscular junction?
Definition
Hemicholinium blocks the re-uptake of choline by the presynaptic terminal

This reduces the amount of ACh that can be synthesized and thus released so NM transmission is decreased
Term
What is myasthenia gravis?
Definition
It is autoimmune disease that affects neuromusclar transmission

In this disease antibodies are produced that attack the nicotinic receptors on the motor end plate

The number of receptors is decreased as well as the in-folding of the membrane

Treatment of this disease can involve increasing ACh levels - example through the use of physostigmine and other anticholinergics (neostigmine) or using immunosuppressive drugs (to lower the antibodies)

ONLY the postsynaptic is affected (no problems with ACh synthesis or release)
Term
What happens in denervation at the neuromuscular junction?
Definition
When a muscle nerve is severed, there is an immediate paralysis of that muscle.

The muscle membrane potential then decreases,

TTX-insensitive channels appear on the muscle membrane, and ACh receptors appear outside the neuromuscular
junction.

This causes the muscle to be hypersensitive to ACh and there may be spontaneous fibrillation and twitching.

Eventually the muscle atrophies due to the loss of the trophic action of its nerve supply.

Changes can be reversed by reinnervation