Physiology: Physiology of the Skeletal Neuromuscular Junction

Question 1

How do ‘curare-like’ compounds reduce the endplate potential to below the muscle fibre threshold potential?

Answer 1

Act as competitive antagonists of nAChr so interfere with the postsynaptic action of ACh

Question 2

Name the enzyme that catalyses the synthesis of ACh from choline and acetyl CoA at the pre-synaptic terminal

Answer 2

Choline acetyltransferase

Question 3

Describe the structure of nicotinic ACh receptors

Answer 3

Pentamers of glycoprotein subunits surrounding a central cation selective pore

Question 4

Name the enzyme that hydrolyses ACh into choline and acetate at the endplate membrane

Answer 4

Acetylcholinesterase (AChE)

Question 5

Describe the summation of miniature endplate potentials and the initiation of contraction

Answer 5

Many miniature end plate potentials summate to produce the endplate potential

If the endplate potential exceeds the threshold, voltage gated Na+ channels will open and the action potential will initiate muscle contraction

Question 6

Define a motor unit

Answer 6

The neurone and and the number of muscle fibres it innervates

Question 7

What is the function of Ca2+ at the pre-synaptic terminal?

Answer 7

Resulting in migration of the neurotransmitter storage vesicles to the active zones at the presynaptic membrane

Question 8

What is the function of the vesicular ACh transporter?

Answer 8

Concentrates ACh into vesicles at the pre-synaptic terminal

Question 9

What causes Lambert-Eaton Myasthenic Syndrome?

Answer 9

Antibodies against voltage-activated Ca2+ channels in the motor neuron terminal result in reduced Ca2+ entry in response to depolarisation → reduced ACh release

Question 10

What is a vesicle?

Answer 10

Secretory organelle that ACh is stored in at the pre-synaptic terminal

Question 11

How is the end plate potential generated?

Answer 11

ACh opens many simultaneous nACh receptors leading to depolarising Na+ influx

Question 12

What causes Myasthenia Gravis?

Answer 12

Autoantibodies against nAChr in the endplate results in reduction in the number of functional channels → amplitude of endplate potential decreases

Question 13

How does the muscle action potential cause contraction?

Answer 13

When the action potential reaches the T tubules, Ca2+ is released from the sarcoplasmic reticulum

Question 14

Why are voltage-activated Na+ channels required at the endplate?

Answer 14

Having a muscle fibre with voltage activated Na+ channels means that the action potential propagates from the endplate over the length of the muscle fibre so contraction occurs

Question 15

How many ACh molecules are needed to activate one ACh receptor?

Answer 15

2

Question 16

What causes acquired neuromytonia?

Answer 16

Antibodies against voltage-activated K+ channels in the motor neurone disrupt functioning resulting in hyperexcitability and repetitive firing

The endplate potential is prolonged and there is repetitive potential discharge in skeletal muscle fibres

Question 17

Name the neuron type that innervates skeletal muscle

Answer 17

Myelinated ⍺-motoneurones

Question 18

Describe the action of botulinum toxin

Answer 18

Enters presynaptic terminals to enzymatically modify proteins involved in the docking of vesicles containing ACh to the presynaptic membrane, which prevents exocytosis

Question 19

What triggers the influx of Ca2+ in the pre-synaptic terminal?

Answer 19

Voltage-gated Ca2+ channels opened by depolarisation of the action potential