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ESA 1 - ICPP > Synaptic Transmission > Flashcards

Flashcards in Synaptic Transmission Deck (16)
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1
Q

What is a neuromuscular junction?

A

Synapse between a nerve and a skeletal muscle fibre.

2
Q

What is the main difference between a nerve terminal and the rest of the axon?

A

High density of voltage-gated calcium channels.

3
Q

Which ion channels are present in the nerve terminal?

A
  • Voltage-gated Na+ channels
  • Voltage-gated K+ channels
  • Voltage-gated Ca2+ channels
4
Q

Describe the structure of voltage-gated calcium channels.

A
  • Structure of alpha-subunit of VOCC is very similar to voltage-gated Na+ channel: 1 peptide with 4 voltage-sensing domains = functional pore-forming subunit.
  • Other associated subunits fine tune the properties and enable correct regulation of channel activity.
5
Q

How can the activity of VOCC be regulated?

A
  • Phosphorylation
  • E.g. NA activates beta1 GPCR - Gs - AC - PKA pathway in cardiac ventricles leading to PKA phosphorylating VOOCs to increase calcium entry into myocytes for increase inotropy.
6
Q

Describe the process of calcium channel inactivation.

A
  • VOCCs inactivate (and activate) more slowly than voltage-gated Na+ channels.
  • VOCC inactivation is calcium-dependent: increased intracellular calcium leads to VOCC inactivation through:
    • direct binding of Ca2+ to the VOCC-calmodulin complex
    • Ca2+ mediated dephosphorylation of VOCC
    • Ca2+ dependent disruption of connection between VOCC and cytoskeleton
7
Q

Describe the process of NT release from the pre-synaptic membrane.

A
  1. Nerve membrane depolarisation - calcium entry through VOCC.
  2. Ca2+ binds to synaptotagmin (involved in synaptic vesicle docking and fusion).
  3. NT vesicle brought closer to membrane - SNARE complex makes a fusion pore.
  4. NT released through pore.
8
Q

How can the amount of NT released be increased?

A
  • Increase frequency of APs - increases amount of nerve terminal Ca2+ entry - increases signal strength.
9
Q

Describe the generation of an AP by ACh.

A
  1. ACh released from the pre-synaptic terminal diffuses across the synaptic cleft.
  2. 2 ACh bind to nicotinic ACh receptor - conformational change in receptor - causes cation-selective pore opening.
  3. Na+ enters cell, K+ exits cell through pore at equal rate.
  4. Membrane depolarisation.
  5. ACh degraded quickly by ACh esterase.
10
Q

Why is membrane depolarisation generated by the entry/exit of Na+/K+ through pore at equal rate?

A
  • Membrane is already close to K+ equilibrium - driving force for K+ to exit is smaller than force for Na+ to enter.
11
Q

How does an AP generate muscle fibre contraction?

A
  • Brief depolarisation initiated close to end plate activates adjacent Na+ channels due to local spread of charge - muscle AP.
  • AP propagates along fibre and initiates contraction of skeletal muscle.
12
Q

How can muscle contraction by blocked?

A
  • By blocking nicotinic ACh receptors - nerve cell cannot pass on electrical signal to muscle cell.
13
Q

What are the 2 main types of nAChR blockers?

A
  1. Competitive blocker
    E.g. Tubocurarine - prevents ACh binding (although block by d-TC can be overcome by increasing ACh concentration).
  2. Depolarising blocker
    E.g. Succinylcholine - binds and activates nAChR but maintains depolarisation state - initial contraction but will fail to activate adjacent Na+ channels as they will become inactivated.
14
Q

Name a disease involving nAChRs?

A

MYASTHENIA GRAVIS

15
Q

What is myasthenia gravis?

A
  • Autoimmune disease where antibodies are directed against nAChR on post-synaptic membrane of skeletal muscle.
  • Leads to loss of functional nAChR by complement-mediated lysis and receptor degradation.
  • Endplate potentials are reduced in amplitude and fail to reach threshold - muscle weakness and fatigue.
16
Q

Compare the roles of nAChRs and mAChRs.

A

nAChR

  • Ligand-gated R on skeletal muscle
  • Produces fast depolarisation because it is ligand-gated ion channel.

mAChR

  • GPCR on membrane of target tissue in parasympathetic autonomic nervous system.
  • Produces slower response as is coupled to G proteins which trigger a cascade of events in the cell.