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Physiology and Pharmacology of Cells > L12 - Ion Channels and Muslce Contraction > Flashcards

L12 - Ion Channels and Muslce Contraction Flashcards

1
Q

What is the structure of muscles?

A

Sarcomeres –> myofibril –> fibre –> fascicle

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2
Q

What is cross bridge theory?

A

Tension generated in muscle is dependent on the area of overlap between actin and myosin
The greater the area of overlap, the more cross bridges can form
- Brings the Z lines closer together

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3
Q

What is the sliding myofilament hypothesis?

A

Neuronal action potential in motor neuron
Leads to muscle action potential
Activation of voltage gated Ca channels - increased intracellular Ca2+
Myofilments slide leading to muscle contraction

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4
Q

What is a motor unit of the neuromuscular junction?

A

The motor neurone and all the muscle fibres it innervates

  • Muscles have multiple motor units
  • Defines fine muscle control
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5
Q

A motor unit with more muscle fibres allows?

A

A more finely graded contraction – spatial summation

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6
Q

What are the 4 key channels of the neuromuscular junction?

A

Voltage gated Na channel - pre and post synaptically
- Depolarisation
- Depolarisation caused by Ach triggers opening and closing of these Na channels
Voltage gated K channel – pre and post synaptically
- Repolarisation
Voltage gated Ca channels - pre and post synaptically
- Triggers release of Ach containing vesicles
Ach receptor – post synaptically

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7
Q

Skeletal muscle action potential characteristics?

A

Same as neuronal action potentials
- Some differences in voltage-gated ion channel family members
Takes 1-2 ms

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8
Q

What is the nicotinic AchR selective for?

A

A non-selective ligand-gated cation channel – Na, Ca and K

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9
Q

Nicotinic AchR Nernst potential?

A

0 mV

Half way between Na and K Nernst potentials

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10
Q

What is the role of the nicotinic AchR?

A

Causes depolarisation
This depolarisation causes opening of voltage gated Na channels
It alone is not enough to trigger an action potential

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11
Q

What is the structure of the nicotinic AchR?

A

4 types subunits
5 subunits needed to make receptor – pentameric (2 alpha subunits)
- Can have different receptors with a different mix of subunits
2 binding sites for Ach
4 transmembrane spanning domains

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12
Q

What is the gating process of the nicotinic AchR?

A

Closed
Closed – 1 agonist bound
Closed – 2 agonists bound
Open – both binding sites have to have Ach bound to open the channel

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13
Q

What are the genes coding for the alpha subunit of the nicotinic AchR?

A

CHRNA1
9 different genes coding for alpha subunits
- CHRNA1 – found in skeletal muscle
- CHRN2-8 - found in neuronal tissue

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14
Q

What are the genes coding for the beta subunit of the nicotinic AchR?

A

CHRNB1
4 different genes coding for beta subunits
- CHRNB1 – found in skeletal muscle
- CHRNB2-4 – found in neuronal tissue

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15
Q

What is Myasthenia gravis?

A

Autoimmune disease - NMJ disorder

2-7 in 10,000 UK

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16
Q

What causes Myasthenia gravis?

A

Antibodies made against AchR on postsynaptic membrane of NMJ
Lead to a block and degradation of AchR

17
Q

What are the symptoms of Myasthenia gravis?

A

Weakness and tiredness in skeletal muscles
Can be fatal – respiratory failure
Females peak incidence – 30s
Males peak incidence – 60-70s

18
Q

What is the antibody evidence for myasthenia gravis?

A

87% of patients positive for antibodies
Injection of mice with antibodies to AchR – experimental MG
- Loss of ability to contract muscle

19
Q

What are the 6 different treatments for myasthenia gravis?

A 
Acetycholinesterase inhibitors
Immunosuppressants - corticosteroids
Immunosuppressants – other 
IV immunoglobulins
Plasmapheresis
Thymectomy
20
Q

Acetylcholinesterase inhibitors overview

A

E.g. Pyridostigmine
Use - mild
Block breakdown of Ach - enhances Ach levels

21
Q

Immunosuppressants - corticosteroids overview

A

E.g. Prednisolone
Use - moderate to severe
Immunosuppressant that reduces antibody levels
Side effects – downregulates the whole immune system, weight gain

22
Q

Immunosuppressants - other overview

A

E.g. cyclosporin

Reduces antibody levels

23
Q

IV immunoglobulins overview

A

Use - severe
400mg/kg for 5 days
Mops up antibodies reducing levels

24
Q

Plasmapheresis overview

A

E.g. filtration, immunoadsorption
Use - when acute intervention needed
Removal of antibodies from the plasma – reduces antibody levels

25
Q

Thymectomy overview

A

Use - tumour removal or severe

Removal of AchR antibody secreting B cells

26
Q

What are transverse tubules?

A

Specialist skeletal/cardiac muscle structures
Membrane invaginations important for action potential propagation into myofibrils
Stimulates the release of Ca from sarcoplasmic reticulum – Ca store

27
Q

What are the two types of Ca channel found in the neuromuscular junction?

A

Transverse tubule membrane – L-type Ca channel

Ryanodine receptors

28
Q

L-type Ca channel overview

A 
Clusters of 4 
Voltage gated 
Activation 
- Allows Ca to move from extracellular fluid into the cell 
- Opens ryanodine receptor
29
Q

Ryanodine receptor overview

A

A type of Ca channel
Stimulate Ca release from sarcoplasmic reticulum
- Moves into cytoplasm leading to contraction

30
Q

Ca channels in skeletal muscle

A

Mechanical coupling is the main driver of opening ryanodine receptors
A few Ca channels will open because of the influx of Ca through L-type receptors

31
Q

Ca channels in cardiac muscle

A

Ca induced Ca release is the main driver of opening ryanodine receptors

32
Q

What are the 2 ways Ca is reup taken by the cell membrane?

A

Ca ATPase
- Pump Ca out in exchange for halogen ions
Na/Ca exchanger
- Pump Ca out in exchange for Na

33
Q

What are the 2 ways Ca is reup taken by the sarcoplasmic reticulum membrane?

A

Ca ATPase
- Pump Ca in in exchange for halogen ions
Calreticulin and calsequestrin
- Ca binding
- Acts as a calcium buffer within the sarcoplasmic reticulum

Physiology and Pharmacology of Cells (13 decks)

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