pharmacology of neuromuscular junction

Question 1

where are motor neurone cell bodies found

Answer 1

in either spinal cord or brain stream

Question 2

how is skeletal muscle innervated

Answer 2

by motor neurons with myelinated axons

the motor neurone divides into unmyelinated branches near to the muscle, each branch innervates an individual skeletal muscle cells forming the motor unit

individual branches further divide into multiple fine branches each ending in a terminal bouton that forms a chemical synapse at the neuromuscular junction

Question 3

what neurotransmitter is released at the neuromuscular junction

Answer 3

acetylcholine

Question 4

where does the presynaptic terminal (buuton) synapse

Answer 4

at the endplate region of skeletal muscle fibres (post-synaptic)

Question 5

what is the presynaptic terminal (bouton) surrounded by

Answer 5

Schwann cells

Question 6

what is the synaptic cleft

Answer 6

small gap over which the neurotransmitter diffuses before encountering the nicotinic ACh receptors

Question 7

where is the ACh released from

Answer 7

synaptic vesicles

Question 8

where do vesicles queue up to release ACh

Answer 8

active zones

Question 9

what is an overview of synaptic transmission in the neuromuscular junction

Answer 9

1. synthesis of ACh
2. storage of ACh by vesicles
3. Release of ACh into synaptic cleft
4. Receptor activation on the end plate
5. transmitter inactivation

Question 10

what is ACh synthesised from

Answer 10

choline and acetyl coA

Question 11

What enzyme synthesises ACh

Answer 11

choline acyetyltranderase

Question 12

what does arrival of the action potential at the pre-synaptic terminal cause

Answer 12

1) depolarisation and opening of Ca2+ channels

2) allows Ca2+ entry to the terminal

Question 13

what does Ca2++ do at the pre-synaptic terminal

Answer 13

causes vesicles to fuse with presynaptic membrane (exocytosis) allowingg ACh to diffuse into the synaptic cleft

Question 14

what does the ACh activate on the post synaptic end plate

Answer 14

nicotinic ACh receptors

Question 15

how are nicotinic ACh receptors assembled

Answer 15

as a pentameter of glyocpotein subunits that surround a central pore.

The pore contains a gate that is closed in the absence of ACh but opens when to ACh molecules bind to the outside of the receptor.

Question 16

what does the nicotinic ACH receptor do when its switched on

Answer 16

when gate is open Na+ enters the muscle cell, whilst K+ exits

the influx of Na+ is greater than the efflux of K+ therefore a depolarisation known as end plate potential is generated (Excess +ve charge makes the muscle depolarised (become less negative))

Question 17

what is a miniature end plate potential

Answer 17

a tiny depolarisation of the end plate region caused by one quantum of transmitter being released from one vesicle

Question 18

what forms the end plate potential

Answer 18

lots of miniature end plate potentials summated due to lots of vesicles releasing quantums of neurotransmitters at the same time

Question 19

as long as the end plate potential is big enough there is an action potential and muscle contraction true/false

Answer 19

true

Question 20

how do you get muscle weakness/paralysis from drugs

Answer 20

drugs effect end plate potential stopping it from reaching the threshold to open the ACh nicotinic receptors to produce an action potential

Question 21

what is acetylcholinesterase

Answer 21

an enzyme which hydrolysis ACh therefor terminates its action

Question 22

what is neuromyotomia

Answer 22

disease where the function of voltage activated potassium channels in the motor neurone axon and terminal doesn’t work

skeletal muscle fibres are over stimulated

Question 23

symptoms of neuromyotmia

Answer 23

cramps
stiffness
slow relaxation (myotonia)
muscle twitches (fasciculation’s)

Question 24

how do you treat neruomytomia

Answer 24

anti-epileptic drugs which block voltage activated sodium channels

Question 25

what is Lambert Eaton Myasthenic syndrome

Answer 25

characterised by muscle weakness in limbs and associated with small cell carcinoma in the lungs

autoimmune origin

not enough ACh in the cleft

Question 26

treatment for Lambert-eaton syndrome

Answer 26

anti cholinesterase - increases the concentration of ACh in the cleft by blocking enzyme which gets rid of it

Question 27

What is myasthenia gravis

Answer 27

progressively increasing muscle weakness during periods of activity

often weakness of eye and eyelid

autoimmune

Question 28

what is the mechanism of myasthenia gravis

Answer 28

antibodies against nicotinic ACh receptors in the end plate result in a reduction in the number of functional channels and hence the amplitude to the end plate potential

Question 29

drug treatment for myasthenia gravis

Answer 29

anticholinesterases which increase the concentration of ACh in the synaptic cleft

Question 30

what is botulinum toxin

Answer 30

extremely potent toxin that irreversibly inhibits Ach release

Question 31

how can botulinum toxin be used clinically

Answer 31

low dose botulinum can be administered to treat overactive muscles