Senses (JAP lectures)

Question 1

What is the structure of a motor unit?

Answer 1

Motor neurone axon divides into unmylinated branches, each branch innervates a muscle fibre at a neuromuscular junction.

Each individual branch divides ending in terminal BOUTON that forms a chemical synapse with the muscle membrane.

Question 2

What is the structure of the skeletal neruomuscular junction?

Answer 2

Terminal bouton and surrounding schwann cell. Contains synaptic vesicles (with Ach in them) which cluster at ACTIVE ZONES.
articulates with muscle via synaptic cleft at the muscle’s END PLATE REGON - which is in JUNCTIONAL FOLDS

Question 3

What is the presynaptic process of Ach transmission?

Answer 3

1. Choline transported into the terminal by choline transporter - this a symport with Na+
2. Ach is synthesized in the cytosol from from choline, acetyl coenzyme A and the enzyme choline acetyltransferase (CAT)
3. ACh is concentrated in vesicles by the vesicular ACh transporter
4. Arrival of AP allows depolarization and opening of voltage activated Ca2+ channels
5. Ca2+ causes vesicles to fuse with presynaptic membrane via exocytosis, Ach diffuses into the synaptic cleft and activates post synaptic nicotinic recepetors in endplate region

Question 4

What is the post synaptic process of Ach transmission?

Answer 4

1. The presence of TWO ach molecules binfing to exterior of nictonic ach receptor opens the gate of it
2. The open channel is permeable to Na+ and K+
3. Na+ influx, K+ efflux
4. The driving force of Na+ greater than K+. This causes END PLATE POTENTIAL generation (depolarization.

Question 5

What are the glycoprotein subunits in the nictotinic Ach receptor in adult muscle?

Answer 5

Two alpha, one delta, one beta and one epsilon

These come together to form the conducting pathway

Question 6

What is a minature end plate potential?

Answer 6

Depolarization in response to one “quantom” of neurotransmitter
- this is the amount of ach in ONE vesicle

Question 7

What is end-plate potential?

Answer 7

A graded electrotonic response

Question 8

Many m.e.p.ps summate to produce ?

Answer 8

end-plate potential

Question 9

An e.p.p that exceeds threshold triggers ?

Answer 9

an ‘all or none’ propagated action potential that initiates contraction

Question 10

One ction potential in the muscle causes a subsequent?

Answer 10

‘twitch’ or contraction of the muscle

Question 11

Why are voltage activated Na+ channels along the length of the muscle fibre important for contraction?

Answer 11

Because they allow the action potential to propagate from the endplate over the length of the muscle fibre

otherwise would decline as it spreads

Question 12

Action potential propagates over the surface membrane (-) of skeletal muscle fibre and enters transverse -
- (invaginations of the - that dip deeply into the muscle cell). T-tubules are in close apposition to the - -.

Answer 12

sarcolemma, T tubules, sarcolemma , sarcoplasmic reticulum

Question 13

Action potential arriving at the - - triggers release of - from the - - which in turn causes contraction by interacting with - .

Answer 13

T-tubules, Ca2+, sarcoplasmic reticulum, troponin

Question 14

Rapid termination of neuromuscular transmission is the result of - of ACh by -, an enzyme associated with the end plate membrane

Answer 14

HYDROLYSIS

acetylcholinesterase (AChE)

Question 15

How is Ach reuptaken into the buton?

Answer 15

hydrolysed by ACETYLCHOLINESTERASE into chloine and acetate
Choline is taken up by choline transporter
Acetate diffuses from the synaptic cleft

Question 16

Ach hydrolisation by acetylcholinesterase is extremely slow

Answer 16

F

some Ache hydrolyses Ache prior to binding to nicotinic receptors… VERY EFFCIENT

Question 17

Which aspect of the neuromuscular junction does neuromyotonia affect? What is the effect of this?

Answer 17

The Na+ symporter on the bouton

- Has autoimmune component which results in hyperexciteability

Question 18

Which aspect of the neuromuscular junction does Lambert-Eaton Myasthenic Syndrome affect?

Answer 18

Calcium channel near active zone on bouton

- Autoimmune component against Ca2+ channels, reduced entry of Ca2+ and reduced vesicular release

Question 19

Which aspect of the neuromuscular junction does Myasthenia Gravis affect?

Answer 19

The nicotinic Ach receptors
- antibodies against nicotinic receprots results in reduction of functioning channels and recudtion in amplitude of epp and AP

Question 20

Which aspect of the neuromuscular junction does Botulinum Toxin affect? How?

Answer 20

The vesicles of Ach at the active zone

- toxin enzymatically modifies proteins involved in docking of Ach vesicles and irreversibly inhibits Ach release

Question 21

What are the symptoms of neuromyotonia?

Answer 21

cramps, stiffness, slow relaxation (myotonia), and muscle twitches (fasiculations)

Question 22

Which drugs are used to treat neuromyotonia?

Answer 22

anti-convulsants (e.g. carbamazepine, phenytoin) which block voltage-activated Na+ channels

Question 23

What are the main characteristics of Lambert-Eaton Myasthenic Syndrome?

Answer 23

Characterised by muscle weakness in the limbs, very rare and associated with small cell carcinoma of the lung

Question 24

Which drugs are used to treat Lambert-Eaton Myasthenic Syndrome?

Answer 24

anticholinesterases (e.g. pyridostigmine) and potassium channel blockers (e.g. 3,4-diaminopyridine) which increase the concentration of ACh in the synaptic cleft

Question 25

What are the main characteristics of myasthenia gravis?

Answer 25

• progressively increasing muscle weakness during periods of activity (fatiguability, contrast with LEMS that may transiently improve upon exertion).
• Often weakness of the eye and eyelid muscles is a presenting feature

Question 26

What is the drug treatment for myasthenia gravis?

Answer 26

• anticholinesterases, to increase the concentration of ACh in the synaptic cleft
• immunosuppressant agents (e.g. azathioprine).

Question 27

What diseases is botulinum toxin associated with?

Answer 27

Tetanus, diphtheria toxins

Question 28

anti cholinesterases can be used as treatment against botulinum toxin

Answer 28

F

Question 29

Botulinum toxin has cosmetic uses

Answer 29

T

- Smoothing out age-related wrinkles

Question 30

What is a clinical use of botulinum toxin?

Answer 30

At low doses can be used to treat over active muscles e.g. extraocular muscles in squints