M&R 5.1 - Cellular Response to Action Potentials

Question 1

How do action potentials open vg Ca2+ channels?

Answer 1

• Depolarisation = opening

- Ca2+ influx inwards due to large concentration gradient

Question 2

Describe the structure of vg Ca2+ channels

Answer 2

• Very similar to Na+ channels (specifically the alpha subunit, the pore forming subunit)
• 4 repeats with a voltage sensor
• Some repeats have phosphorylation sites which alter its activity e.g. cardiac muscle

Question 3

Describe the diversity of vg Ca2+ channels

Answer 3

• Very diverse
• Found in skeletal muscle, neurones, lungs etc.
• L types are clinically relevant

Question 4

Why are L-type vg channels clinically relevant?

Answer 4

They can be targeted due to their different structures and are susceptible to blockers

Question 5

What is the function of the mitochondria at the motor end plate?

Answer 5

Remove residual Ca2+ that is left over from the action potential

Question 6

What is the function of Acetylcholinesterase at the motor end plate?

Answer 6

Quickly breaks down Acetylcholine

Question 7

What is the function of vesicles at the motor end plate?

Answer 7

• Contain a high concentration of Acetylcholine

- Ca2+ influx due to action potenital = release of Ach by exocytosis

Question 8

Describe the process of transmitter release from a vesicle

Answer 8

• Ca2+ entry through Ca2+ channels
• Ca2+ binds to synaptotagmin (Ca2+ channels close)
• Vesicle brought close to membrane due to binding
• Snare complex make a fusion pore causing vesicle to be continuous with the extra cellular space
• Transmitter released through this pore

Question 9

What happens after Ach has been released into the synaptic cleft?

Answer 9

• Ach diffuses across and binds to the nicotinic Ach receptors on the post-junctional membrane
• Produces an end-plate potential
• Excess is broken down by Acetylcholinesterase

Question 10

What happens after the binding of the Ach to the nicotinic receptors?

Answer 10

• End plate potential is produced due to depolarisation (K+ exit is overcome)
• Raises membrane potential closer to Ena

Question 11

Describe the structure of a nicotinic Ach receptor

Answer 11

• 2 alpha subunits
• 5 subunits
• Binds 2 molecules of Ach to cause a conformational change

Question 12

Describe the action of competitive antagonists such as Tubocurarine on nicotinic Ach receptors

Answer 12

• Similar structure to Ach so sits in binding site
• Doesn’t produce a conformational change so remains closed (doesn’t activate)
• Reversible so can be overcome by a high Ach concentration

Question 13

Describe the action of depolarising blockers such as Succinylcholine on nicotinic Ach receptors

Answer 13

• Binds and activates nicotinic receptors
• Maintains depolarisation
• Causes accommodation to happen so Na+ channels are inactive

Question 14

What is Myasthenia Gravis? How does it present?

Answer 14

• An autoimmune disease targeting nAch receptors

- Profound weakness that increases with exercise

Question 15

What mechanism of action for myasthenia gravis?

Answer 15

• Antibodies are directed against nAChR on postsynaptic membrane of skeletal muscle
• Loss of functional nAChR by complement mediated lysis and receptor degradation
• End plate potentials are reduced in amplitude leading to muscle weakness and fatigue

Question 16

What is a miniature end-plate potential?

Answer 16

• Spontaneous release of 1 vesicle therefore releasing Ach

- Doesn’t reach threshold so an action potential is not activated

Question 17

How is Myasthenia Gravis diagnosed?

Answer 17

• Measure miniature end plate potential as it shows receptor deficiency

(not enough receptors to be activated to generate a big enough enough potential by calcium influx)