W5 - NMJ And Control Of Muscle Contraction

Question 1

What is the NMJ?

Answer 1

A synapse between a motor neurone and muscle cell

Question 2

How is the presynaptic terminal specialised?

Answer 2

Contains a high number of synaptic vesicles which are lined up and ready to be released at the active zone of the presynaptic terminal.

Question 3

How is the postsynaptic membrane specialised?

Answer 3

Many junctional folds to increase the surface area of the postsynpatic membrane. Also expresses lots of receptors.

Question 4

What is guaranteed at the NMJ?

Answer 4

A synaptic event WILL cause activation postsynaptically.

Question 5

Does the NMJ axons branch a lot?

Answer 5

Yes and each has a synaptic terminal for point of neurotransmitter release at motor end plate regions.

Question 6

What is the neurotransmitter at the NMJ?

Answer 6

Acetylcholine. One vesicle contains a single quanta.

Question 7

What is the role of calcium ions in excitation-contraction coupling?

Answer 7

An AP occurs at the presynaptic terminal depolarising the membrane, opening VGCa2+ channels. This causes an influx of Ca2+ into the presynaptic terminal, which triggers the movement of vesicles towards the presynaptic membrane, release ACh by exocytosis into the synaptic cleft. (Ca2+ sensor is synaptotagmin which undergoes a conformational change on Ca2+ binding, triggering vesicle fusion)

Question 8

What is the receptor at the end-plate of the NMJ?

Answer 8

Nicotinic ACh receptor. Membrane spanning protein made of 5 subunits, with two binding sites for ACh. Ionotropic or ligand-gated ion channel.

Question 9

How does ACh cause depolarisation?

Answer 9

ACh binds to nicotinic receptors on the postsynaptic end-plate membrane. Two must bind to cause the conformational change to allow the opening of the channel. Inside of the cell gets depolarised by Na+ influx (which is greater than K+ efflux). Excitatory effect.

Question 10

What is the RMP of a NMJ?

Answer 10

-90mV

Question 11

What is an end plate potential EPP?

Answer 11

An individual electrical event that will trigger the opening of the voltage gated channels which triggers the action potential which is a separate electrical event. It is -20mV.

Question 12

How does EPP change as it moves away from the end-plate?

Answer 12

It decays as it moves away from the end-plate because nAChRs are absent from the synapse and only present postsynaptically at the motor end plate. The action potential can spread all through the muscle fibre though.

Question 13

Properties of the EPP

Answer 13

Timing: presynaptic AP to EPP is approx 1ms
EPP generated by ligand-gated channels to cause VG channel opening
EPP is very large due to many ACh vesicles and high density of nAChRs
Threshold for AP generation is easily passed

Question 14

What does the AP invade at the postsynatpic terminal?

Answer 14

AP invades T (transverse) tubule system. Allows the transmission of AP deep into muscle fibre and to separate myofibrils.

Question 15

How does the sarcoplasmic reticulum allow intracellular calcium levels to be increased?

Answer 15

• DHP (dihydropyridine) receptor (an L-type VGCa2+ channel) is triggered to open by an AP
• the DHP receptor is tethered to a Ca2+ release channel = ryanodine ‘receptor’
• channel opens and calcium is released into the intracellular space of the myofibril
• after the AP has passed, repolarisation occurs and the channels are shut, and calcium is pumped back into the SR and bound to calsequestrin.

Question 16

Does a full contraction always occur?

Answer 16

Contraction will always occur but might not necessarily be a full contraction since only one NMJ is activated which is attached to one fibre.

Question 17

How is a full sustained and coordinated contraction produced?

Answer 17

Activation of NMJs coordinated across multiple motorneurones and muscle fibres to produce a sustained and coordinated contraction of a muscle. High rate of firing needed for individual twitches to join together and cause sustained muscle contraction. Pic at 35:10.

Question 18

Fate of ACh after binding.

Answer 18

The signal must be switched off so acetylcholinesterase (AChE) rapidly hydrolyses ACh into choline and acetate. Presynaptically the neurone has the ability to uptake the choline, which is used to form more ACh.

Question 19

What is myesthenia gravis?

Answer 19

Characterised by muscle weakness during sustained activity. First exhibited in eyes since they are most active in the body. Autoimmune disease of nAChR - reduced numbers at the NMJ, so synapse fails.

Question 20

What is treatment of MG?

Answer 20

Treatment is AChE inhibitors because it prolongs the signal, e.g., neostigmine

Question 21

Relationship between muscle firing and tension in response to nerve stimulation.

Answer 21

Muscle firing causes a certain amount of tension in the muscle.

Question 22

What happens to the muscle firing and tension in MG?

Answer 22

In MG their individual APs are compound in the muscle, caused by multiple synapses all firing at once. Some are failing but the AP gets progressively smaller due to a deficit in the number of receptors which are being activated by ACh. Thus a decrease in muscle tension and muscle contraction is not sustained. Effects reversed by neostigmine. Pic at min 41.