YW - NMJ

Question 1

What does the Autonomic Nervous System (ANS) regulate? (4)

Answer 1

Regulates:

• Smooth muscles
• Exocrine glands
• Cardiac tissue
• Metabolic activities

Involuntary
Regulated by brain stem centres

Question 2

What is the Somatic Nervous System responsible for?

Answer 2

Activates:

• Skeletal muscle contraction

Voluntary body movements

Regulated by corticospinal tracts and spinal reflexes

Question 3

Where does acetylcholine act in the sympathetic and parasympathetic nerves?

Answer 3

Acetylcholine acts on nicotinic receptors in the:

• SYMPATHETIC nerve (N2)
• SOMATIC nerve (N1)

Acetylcholine acts on nicotinic receptors and muscarinic receptors in the PARASYMPATHETIC nerve

Question 4

Ach Synthesis (2)

Answer 4

1) PYRUVATE → Acetyl-CoA + Choline

• Pyruvate Dehydrogenase

2) Acetyl-CoA + choline → Acetylcholine

• Choline acetyltransferase

Question 5

Ach Degradation

Answer 5

Acetylcholine → Acetate + choline

• Acetylcholinesterase

Question 6

What subtypes are present in Nm (muscle) and Nn (neuronal) receptors?

Answer 6

Nm receptors contain:

• alpha-1 subtype
• beta-1 subtype
• plus delta and gamma/epsilon (embryo/adult)

Nn receptors contain:

• alpha(2-10) subtype
• beta(2-4) subtype

Question 7

Describe the structure of the Ach receptor and the presence of the binding site

Answer 7

Heteropentamer containing 4 polypeptide chains

• 2x α subunits
• 1x β subunit
• 1x γ subunit
• 1x δ subunit

Ach binding site located between α and γ subunit and α and δ subunit

Question 8

What is the Neuromuscular Junction (NMJ)?

Answer 8

A specialised form of synaptic transmission: communication between neurons and skeletal muscle

Question 9

What occurs after binding of Ach to Ach receptors on the post-synaptic terminal? (3)

Answer 9

1. Binding of ACh to AChRs opens the channels causing an influx of Na+
2. Depolarization of the sarcolemma that travels down the t-tubules
3. Causes the release of Ca2+ from the sarcoplasmic reticulum - CONTRACTION

Question 10

How is unbound ACh in the synaptic cleft removed or inactivated?

Answer 10

Diffuses away or hydrolyzed by acetylcholinesterase (AChE)

Question 11

Neuromuscular Junction Disorders (3)

Answer 11

• Myasthenia gravis
• Lambert-Eaton myasthenic syndrome
• Neuromyotonia (Isaac’s syndrome)

Question 12

What is Myasthenia Gravis (2), and what are its symptoms (3)?

Answer 12

Autoantibodies to the nicotinic AChR on the motor end-plates of muscles

• Binding of ACh is blocked and muscle activation is inhibited.
• The autoantibodies also induce complement-mediated degradation of the AChRs, resulting in progressive weakening of the skeletal muscles

Autoantibodies to MuSK, which is important for the tight clustering of AChRs at the neuromuscular junction .

SYMPTOMS:

• Weakness of eye and oral muscles
• Difficulty in swallowing
• Breathing difficulties

Question 13

What is Lambert-Eaton myasthenic syndrome, and what causes it?

Answer 13

Autoantibodies to presynaptic voltage-gated calcium channel (VGCC)

• These antibodies interfere with the calcium-dependent release of ACh from the presynaptic membrane
• Cause a reduced endplate potential on the postsynaptic membrane, resulting in NMJ transmission failure

Question 14

What is Neuromyotonia (Isaac’s syndrome), and what causes it?

Answer 14

Autoantibodies to presynaptic voltage-gated potassium channel (VGKC)

• Autoimmune neuromyotonia is typically caused by antibodies that bind to potassium channels on the motor nerve resulting in continuous/hyper-excitability

Muscle cannot repolarise