SESSION 7 LT 2 ELECTRICAL EXCITABILITY-SYNAPTIC TRANMISSION AND NMJ

Question 1

NAME THE THREE ION CHANNELS AT THE PRESYNAPTIC TERMINAL

Answer 1

• Vg Na+ Channel
• Vg Ca2+ Channel
• Vg K+ Channel

Question 2

What is the Eq potential value for Ca2+?

Answer 2

ECa= +122 mv

Question 3

What effect does increasing the action potentials have on the NT release?

Answer 3

• Several AP’s sequentially you have more NT release

- Structure of VG Ca2+ channel similar to Vg Na+ channel

Question 4

Give an example of Specific blockers of L- type Ca2+ channels

Answer 4

Dihydropyridines- eg. NIFEDIPINE
Which has a strange mechanisms of action because the ionic form penetrates the plasma membrane
Binds to intramembranous site on L- type Ca2+ channel

Question 5

Describe the structure of Vg Ca2+ Channels

Answer 5

• Can have more than just the alpha subunit
• Protein kinase can increase the activity eg VOCC channels in ionotropy
• Pore forming subunit necessary for a functional channel
• Other associated subunits fine-tune the properties and enable correct regulation of channel activity.

Question 6

Properties of Ca2+ channels

Answer 6

• Vg Ca2+ channels activate and inactivate more slowly than Na+ channels
• Inactivation of Vg Ca2+ channels - is dependent of Ca2+
  It is the increased intracellular Ca2+ concentration which leads to inactivation of Ca2+ channels.

Question 7

TRANSMITTER RELEASE

Answer 7

• Ca2+ entry through Vg Ca2+ channels
• Ca2+ binds to synaptotagmin
• Vesicles brought close to the membrane
• Snare complex makes a fusion pore
• Transmitter released through this pore - binds to nACHr on postsynaptic membrane

Question 8

How DOES depolarisation occurs in the muscle membrane ?

Post synaptically

Answer 8

• Ach = NT binds to nACHr on post junctional membrane
• Produce END PLATE POTENTIAL
• This depolarisation in turn raises muscle above the electrogenic threshold so an AP is produced in the muscle membrane

Question 9

Why is there a greater driving force fo Na at the NMJ?

Answer 9

• NACHr- allows Na+ and K+ to move equally
  The membrane potential for SKM= -90Mv closer to EK which is -75 mV/-70 mV - therefore, hardly any movement K+
• But further from ENa therefore greater driving force for Na this will cause an end plate potential in the muscle

Question 10

What is transmitter release dependent upon and how does this affect the end plate potential?

Answer 10

• Transmitter release dependent on Ca2+ entry

Therefore if decreased external calcium concentration end plate potentials decrease in AMPLITUDE

Question 11

WHAT IS THE RELATIONSHIP BETWEEN AN END-PLATE POTENTIAL AND MUSCLE ACTION POTENTIAL?

Answer 11

• synaptic potential spreads to adjacent part where you have Vg Na+ channels and you will have depolarisation and it will spread along the membrane fibre
• Ach binds to nACHr post junctional membrane - end plate potential raises the muscle above the electrogenic threshold —> AP in the muscle membrane

Question 12

WHAT ARE THE BLOCKERS OF nACHr’s?

Answer 12

• Competitive blocker- Tubocurarine

- Depolarising blocker- Succinylcholine

Question 13

How does d-tubocurarine work?

Answer 13

• Binds to ACH binding sites
• Prevents ACH from binding and opening the port
  BUT Because its competitive binding therefore increase ACH concentration can overcome the d-TC block

Question 14

How does succinylcholine work?

Depolarising blocker

Answer 14

• Maintained depolarisation
• Increased proportion of inactivated Na+ channels
• Fail to activate adjacent Na+ channels

Question 15

WHAT IS MYASTHENIA GRAVIS?

Answer 15

• AUTOIMMUNE DISEASE
• TARGETING nACH receptors
  -Patient suffers from profound weakness
• Weakness increases with exercise
• Caused by antibodies directed against nACHR on post synaptic membrane of skeletal muscle
  Antibodies leads to loss of functional nACHR - by complement mediated lysis and receptor degradation
  End plate potentials are decreased in amplitude = muscle weakness and fatigue.

Question 16

MYASTHENIA GRAVIS LEADS TO PROFOUND MUSCLE WEAKNESS AND it increases with exercise explain why?

Answer 16

• Auto immune disease caused by antibodies against the nACHR on the post synaptic membrane
  Leading to the loss of functional nACHR by complement mediated lysis and receptor degradation
• End plate potentials are decreased in amplitude this leads to muscle weakness and fatigue

Question 17

How can you increase end plate potentials?

Answer 17

By using ACHe INHIBITORS TO INCREASE THE CONC of ACH and this leads to increase the endplate potential to the threshold

Question 18

WHAT IS THE DIFFERENCE BETWEEN nACHR and mAChR ?

Answer 18

Sympathetic - nACHR
Parasympathetic - pre ganglionic - nACHR and post - mAChR
NAChR- Produces fast depolarisation - ligand gated ion channel
MAChR- Produces slower response because coupled to GPCR’s
Triggers a cascade of events in the cell