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Cell Regulation and Cancer > The signal for muscle contraction > Flashcards

The signal for muscle contraction Flashcards

1
Q

What is signal transduction ?

A

Conversion of information from one form to another, e.g. electrical to chemical during neurotransmission at synapses

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2
Q

Skeletal muscle contraction is regulated by ?

A

A Ca2+-dependent thin filament-based regulatory mechanism

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3
Q

Sarcomere Ca2+ concentration is regulated by ?

A

Release and uptake into the sarcoplasmic reticulum (SR)

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4
Q

Motor axons synapse with the muscle fibre at the ?

A

Neuromuscular junction (NMJ)

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5
Q

Explain signal for contraction ?

A
  1. An action potential stimulates voltage-gated Ca2+ channels in the axon to open (1)
  2. The Ca2+ influx causes fusion of vesicles and release of Ach into the synaptic cleft
  3. Ach binds to the NiAchR on the muscle cell plasma membrane (2)
  4. The NiAchR opens, and Na+ ions flow in causing a local depolarisation, activating voltage-gated Na+ channels, leading to an action potential (3)
  5. The AP activates DHP receptors on the T-tubules (4)
  6. In turn, DHPRs activate RyRs on the SR, leading to calcium release (5)
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6
Q

How are neurotransmitters synthesised and stored ?

A

Neurotransmitter synthesised in the cytoplasm and stored in vesicles

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7
Q

How is acetylcholine broken down ?

A

Broken down (hydrolysed) by acetylcholinesterase

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8
Q

What does acetylcholine bind to?

A

Acetylcholine binds to nicotinic ACh receptors on the muscle cell

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9
Q

What are the two main classes of acetylcholine receptor ?

A
  1. Nicotinic = selectively activated by nicotine (from tobacco)
  2. Muscarinic = activated by muscarine (from the mushroom Amanita muscaria)
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10
Q

What is the Nicotinic Ach receptor ?

A

Ionotropic meaning it is directly linked an ion channel (metabotropic receptors use second messengers)

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11
Q

What is a nicotine addiction due to ?

A

The action of nicotine on nACh receptors in the brain

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12
Q

What can influence the neuromuscular junction ?

A

Many toxins/venoms, e.g. sarin

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13
Q

What is Myasthenia gravis ?

A

This is an autoimmune disorder in which antibodies are formed against the nicotinic receptor

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14
Q

What are changes in nAChR expression linked to ?

A

A wide variety of neurological and psychiatric disorders

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15
Q

What 5 subunits contribute to channel ?

A
  1. Two acetylcholine-binding sites (alpha subunits)
  2. One each of beta, gamma and delta
  3. Each subunit has four membrane-spanning α helices, M1–M4
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16
Q

What forms the wall of the channel ?

A

Amphipathic M2 helices - others are hydrophobic to embedded in the membrane

17
Q

What is caused when acetylcholine binds to nAChr ?

A

It causes a rapid influx of sodium, depolarising the membrane

18
Q

What is at the centre of the nAChr receptor ?

A

There is a ring of bulky hydrophobic leucine residues constricting the channel and keeping it closed

19
Q

When acetylcholine binds to nAChr what does it induce ?

A
  • Acetylcholine induces rotation in M2 subunits, moving these leucine residues away and replacing them with polar residues, opening channel
  • Rapid influx of Na+ ions
20
Q

What does membrane depolarisation activate ?

A

It activates voltage-gated sodium channels, causing further influx of sodium, leading too an action potential

21
Q

Where does depolarisation spread to ?

A

It spreads down muscle membranes into T-tubules

22
Q

What does depolarisation activate on the T-tubule membranes ?

A

Dihydropyridine (DHP) receptors

23
Q

What does depolarisation activate on the T-tubule membranes ?

A

Dihydropyridine (DHP) receptors

24
Q

In turn, what do these DHP receptors activate ?

A

Ryanodine receptors (RyR) on the sarcoplasmic reticulum causing opening and release of Ca2+ into cytoplasm

25
Q

What is the largest known ion channel ?

A

Ryanodine receptor Ca2+ channel

26
Q

What do DHPRs sense ?

A

Membrane depolarisation and transmit conformation change to the RyR causing the channel to open and release Ca2+ from the store: excitation-contraction coupling

27
Q

What happens when calcium ions bind to troponin C ?

A
  • It causes the troponin complex to rotate
  • This removes the tropomyosin blockage of the myosin binding sites
  • Myosin can now bind the actin filaments and initiate contraction
28
Q

What does creatine kinase catalyse ?

A

It catalyses the formation of ATP from phosphocreatine and ADP. As a last resort, myokinase can combine 2ADP to make ATP and AMP

29
Q

What is used as energy for resting muscles ?

A

Fats, but these take time to break down

Cell Regulation and Cancer (13 decks)

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