Synaptic Transmission And The Neuromuscular Junction

Question 1

What is a neuromuscular junction?

Answer 1

The synapse between a nerve and a skeletal muscle fibre

Question 2

Which ion channels are present in the nerve terminal?

Answer 2

Voltage gates Na+ channels
Voltage gated K+ channels
Voltage gates Ca2+ channels

Question 3

How is a Ca2+ channel opened and what is the result of Ca2+ influx

Answer 3

Depolarisation opens the channel

Ca2+ influx causes neurotransmitter release

Question 4

What is the significance of the concentration of Ca2+ inside the nerve terminal?

Answer 4

Because the concentration of Ca2+ inside is so low, the Ca2+ influx through Ca2+ channels can raise the internal concentration of Ca2+ significantly.

Question 5

How can the amount of nerve terminal Ca2+ entry be increased?

Answer 5

Increasing frequency of action potentials

Question 6

What subunits are neccessary for a functioning channel?

Answer 6

A pore forming subunit is necessary for a functional channel
Other associated subunits fine-tune the properties and enable correct regulation of channel activity

Question 7

What are the properties of Ca2+ channels?

Answer 7

• Voltage-gated Ca2+ channels activate more slowly than voltage-gated Na+ channels
• Ca2+ channels activate and inactivate – but much more slowly than Na+ channels
• Ca2+ channel inactivation is Ca2+-dependent

Question 8

How can the Ca2+ current in a snail neurone be measured?

Answer 8

Ba2+ ions will pass through the pore of Ca2+ channels
When Ba2+ flows through the channels much less inactivation is seen
Thus increased intracellular [Ca2+] leads to inactivation of Ca2+ channels

Question 9

Outline the steps in neurotransmitter release

Answer 9

• Ca2+ entry through Ca2+ channels
• Ca2+ binds to synaptotagmin
• Vesicle brought close to membrane
• Snare complex make a fusion pore
• Transmitter (ACh) released through this pore

Question 10

What type of receptors are present on the post synaptic membrane?

Answer 10

LGICs
Ligand is ACh
NAChR

Question 11

Outline the immediate events when ACh binds to a receptor on the post synaptic membrane

Answer 11

2 ACh binding sites on NAChR
When binds - conformational change causes pore to open (NAChR activated)
Pore is cation selective - passes Na+ ca2+ and k+
Driving force for k+ is low but high for Na+
A lot of Na+ moves in
Depolarisation - end plate potential
When end plate potential reaches skeletal muscle threshold, skeletal muscle fires AP
Transmitter release is dependent on Ca2+ entry – end plate potentials decrease in amplitude as external Ca2+ is lowered.

Question 12

What happens once depolarisation of the postsynaptic membrane occurs in a neuromuscular junction?

Answer 12

ACh is degraded quickly by ACh esterase
Brief depolarization will activate adjacent Na+
channels due to local spread of charge causing a muscle AP
The muscle action potential is initiated adjacent to the end-plate and propagates along the muscle fibre
The action potential initiates contraction of the skeletal muscle fibre

Question 13

What is curare?

Answer 13

Crude curare is a resinous, dark brown to black mass with a sticky to hard consistency and an aromatic, tarry odour. The name comes from Indian words (woorari, woorali, urari) meaning “poison.”
Curare causes paralysis by blocking the transmission between nerve and muscle

Question 14

Name 2 types of blocker of nAChRs and give an example of each

Answer 14

Competitive blocker - e.g. tubocurarine which is the active component of curare
Depolarising blocker e.g. succinylcholine

Question 15

How do competitive blockers work?

Answer 15

Binding site occupied by blocker so ACh cant bind
ACh competing with blocker (e.g. d-tc)
If conc of ACh increased - can overcome the block

Question 16

How do depolarising blockers work?

Answer 16

Depolarising blockers (e.g. succinylcholine can activate nAChRs - maintaining depolarisation 
Increases proportion of sodium channels in inactivated state around neuromuscular junction - no longer can open  
They block neuromuscular transmission by stopping sodium channels from opening

Question 17

Name and give brief details of a disease affecting the neuromuscular junction

Answer 17

Mayasthenia gravis - an autoimmune disease targeting nACh receptors.
• Patients suffer profound weakness
• Weakness increases with exercise
• Caused by antibodies directed against nAChR on postsynaptic membrane of skeletal muscle
• Antibodies lead to loss of functional nAChR by complement mediated lysis and receptor degredation
• Endplate potentials are reduced in amplitude leading to muscle weakness and fatigue