lecture 4 : the neuromuscular junction

Question 1

what is a neuromuscular junction?

Answer 1

a specialised synapse between a motor neurone and a muscle fibre

Question 2

what are the main structures in the NMJ

Answer 2

• the pre synaptic nerve terminal
• the synaptic cleft
• the post synaptic nerve terminal

Question 3

what is present on the primary synaptic cleft?

what is present on the secondary synaptic cleft?

Answer 3

• ACh receptors are present

- acetylcholinesterases

Question 4

what is the nature of the chemical communication?

Answer 4

unidirectional

Question 5

what is the neurotransmitter for voluntary started muscle?

Answer 5

it is acetylcholine

Question 6

how is the dominant motor neurone chosen?

Answer 6

• in development the motor neurones compete to be the dominant motor neurone

Question 7

what is the mechanism of a neuromuscular junction?

Answer 7

• action potential opens the voltage gated calcium channels
• Ca2+ enters
• Ca2+ triggers the exocytosis of the vesicles
• ACh diffuses into the cleft
• ACh binds to the post synaptic receptors and opens the channels
• local currents flow from the depolarised region and the action potential is triggered and spreads across the surface membrane
• ACh is broken down by acetylcholinesterase enzyme
• the post synaptic response to the ACh ceases

Question 8

what happens at the NMJ at rest?

Answer 8

• at rest individual vesicles release ACH at a very low rate which causes ‘miniature end plate potentials’

Question 9

what are the potentials called when they don’t make an AP?

Answer 9

these are graded potentials

Question 10

what are myofibrils?

Answer 10

• they are covered by the plasma membrane (the sarcolemma)
• T tubules in the centre
• the cytoplasm is called the sarcoplasm
• there is a network of fluid filled tubules
  ( the sarcoplasmic reticulum)
• they extend along the whole length of the myofibre

Question 11

what is the sarcomere?

Answer 11

the cytoplasm of the myofibril

• composed of two parts
• actin and myosin

Question 12

what does the sarcomere look like?

Answer 12

• looks striated due to light and dark bands

Question 13

what do myofilaments consist of?

Answer 13

• dense protein Z discs separate sarcomeres
• dark bands known as A bands (THICK MYOSIN)
• light bans are I bands
  (THIN MYOSIN)
• the myosin and actin filaments overlap
• H zone which is where only thick myosin is present
• M line which is a line of myosin

Question 14

show a diagram of a myofilament:

Answer 14

INSERT PIC

Question 15

show a diagram of a whole muscle fibre :

Answer 15

INSERT PIC

Question 16

what happens to the bands when contraction happens?

sliding filament theory

Answer 16

• during contraction I bands get shorter
• A bands remain the same length
• H zone disappears

Question 17

what is the activation/ relaxation process?

Answer 17

• the action potential propagates along the surface membrane and into the T tubules
• DHPR in the t tubule senses the change in potential and changes shape and links onto the RyR
• this triggers Ca2+ to be released from the sarcoplasmic reticulum
• Ca2+ binds to troponin and this causes tropomyosin to move
• this means cross bridges attach to the actin
• Ca2+ is then actively transported into the sarcoplasmic reticulum whilst the action potentials continue
• when the Ca2+ has declined it dissociates from the troponin and then tropomyosin blocks new cross bridge attachments from being made

Question 18

what are examples of neuromuscular junction disorders?

Answer 18

• botulism
• myasthenia gravis
• Lambert-Eaton myastenic syndrome.

Question 19

what happens in ?botulism

Answer 19

• Botulinum toxin produces an irreversible disruption in stimulation-induced
  acetylcholine release by the pre-synaptic nerve terminal.

Question 20

what happens in myasthenia gravis?

Answer 20

An auto-immune disease caused by production of antibodies against the ACh receptor

Question 21

what happens in Lambert-Eaton myastenic syndrome?

Answer 21

(Associated with lung cancer) An autoimmune disease caused by antibodies directed
against the VGCCs.