Muscle Contraction and Dysfunction

Question 1

What are the three types of muscle?

Answer 1

→ Skeletal
→ Smooth

→ Cardiac

Question 2

How many muscle fibres are there in bundles and what are they called?

Answer 2

→ fasciculi

Question 3

What is the muscle fibre membrane called?

Answer 3

→ Sarcolemma

Question 4

What is a muscle fibre made from?

Answer 4

→ 100s-1000s of myofibrils

Question 5

What does the sarcoplasm contain?

Answer 5

→ glycogen
→ fat

→ mitochondria
→ enzymes

Question 6

What does the sarcoplasmic reticulum do?

Answer 6

→ Release Ca2+

Question 7

What is a sarcomere?

Answer 7

→ a contractile unit

Question 8

What is the anisotropic band?

Answer 8

→ high density band

Question 9

What is the isotropic band?

Answer 9

→ actin filaments

→ titin

Question 10

Describe how the actin myosin binding sites are exposed

Answer 10

→ Troponin forms a complex with tropomyosin
→ When Ca2+ binds to troponin it causes a conformational change to the troponin

→ This causes the tropomyosin to move
→ It exposes the actin-myosin binding sites
→ Allows the myosin head to bind to the actin

Question 11

Describe the sliding filament theory?

Answer 11

Motor neuron stimulates a muscle to contract
→ Release of Ca2+ into the muscle cell

→ myosin has a globular head that ATP binds to
→ ATP is hydrolysed
→ Phosphate bond breaking provides energy for the power stroke
→ releases ADP and an inorganic phosphate
→myosin head is cocked

Question 12

What does the somatic nervous system do?

Answer 12

→ Provides voluntary control over skeletal muscle

Question 13

What are motor neurons?

Answer 13

→ Efferent neurons that innervate muscle

Question 14

What does one motor unit include?

Answer 14

→ A single motor neuron and all the muscle fibres it controls

Question 15

How do motor units regulate the strength of contraction?

Answer 15

Varying how many activated motor units are recruited

Question 16

Describe what happens at a neuromuscular junction when a stimulus is applied?

Answer 16

→ A stimulus from the brain causes an action potential
→ ACh is released

→ ACh binds to receptors and causes depolarisation of the membrane
→ depolarisation moves along the membrane and through T tubules
→ T tubules enter the muscle and cause depolarisation of the SR
→ SR releases Ca2+
→It is released into the cytosol and causes contraction of muscle fibres

Question 17

What are the 2 types of cholinergic receptor?

Answer 17

→ Muscarinic

→ Nicotinic

Question 18

How many molecules of ACh bind to a nicotinic receptor?

Answer 18

→ 2

Question 19

What does a single action potential produce?

Answer 19

→ a single twitch

Question 20

How do you get greater tension within a muscle?

Answer 20

→ if an additional action potential arrives before the muscle relaxes from the first action potential
→ There is summation of the two and greater contraction

Question 21

What is tetanus?

Answer 21

→ When the rate of action potentials is so high that the muscle doesn’t relax between stimuli

Question 22

What is the mutated gene in DMD? (duchenne muscular dystrophy)

Answer 22

→ dystrophin

→allows for cell membrane to be stabilised as contraction happens

Question 23

What is the function of dystrophin?

Answer 23

→ Connects the sarcomere to the plasma membrane

Question 24

Where is the dystrophin gene located?

Answer 24

short arm of the X chromosome

Question 25

What is the difference between Duchenne and Becker disease?

Answer 25

→Duchenne=total loss of dystrophin | →Becker= reduced or dysfunctional dystrophin

Question 26

What are the effects of dystrophic myopathy diseases?

Answer 26

→increased permeability to macromolecules →abnormal permeability is made worse by mechanical stress →Muscle fibre necrosis, fibrosis and fat inflitration

Question 27

What happens to people with DMD?

Answer 27

→ unable to walk by 10-12 years | → death by early to mid 20s

Question 28

What are the effects of a lack of dystrophin?

Answer 28

→ Dysfunction of the sarcolemma stretch → ion pores open and there is increased intracellular Ca2+ → membrane gets torn

Question 29

What is an indication of muscle damage in DMD?

Answer 29

→ CK (creatine kinase) is lost from the cell and goes into the blood → degradation of structural proteins

Question 30

what is creatine kinase needed for?

Answer 30

→ recycling of ATP

Question 31

What enables patients with DMD to walk for longer?

Answer 31

→ corticosteroids like prednisone

Question 32

What is myasthenia gravis?

Answer 32

→chronic autoimmune motor neuron disease → Body makes antibodies against AChRs at neuromuscular junctions → targets alpha-1 subunit

Question 33

How do you treat myasthenia gravis?

Answer 33

→ AChesterases inhibitors

Question 34

What toxin does myasthenia gravis mimic?

Answer 34

botulinum toxin

Question 35

What is multiple sclerosis?

Answer 35

→Immune attack of myelin →Leaky blood brain barrier →Sclerotic lesions

Question 36

What are the manifestations of MS?

Answer 36

``` →Numbness →Tingling →Speech problems →Visual problems →Debilitating muscle weakness ```

Question 37

What cells produce myelin?

Answer 37

→glial | →non-neuronal

Question 38

What are glial cells called in the CNS and PNS?

Answer 38

CNS=form the myelin sheath are called oligodendrocytes | PNS=called Schwann cells

Question 39

What is the AIS?

Answer 39

Axon initial segment

Question 40

What is the function of AIS?

Answer 40

→Sodium entry through channels at the AIS | →serves as the site of action potential firing and helps to maintain neuron polarity.

Question 41

What is the role of nodes of Ranvier?

Answer 41

Rejuvenation of excitation | →Concentration of voltage gated sodium channels

Question 42

What is the purpose of myelin sheath?

Answer 42

→Prevents charge leakage and dissipation of excitation

Question 43

What are the features of non-dystrophic myotonias?

Answer 43

→Delayed relaxation of the muscle after voluntary contraction or mechanical stimulation. →highly organized repetitive electrical activity of the muscle fibres

Question 44

What mutations characterise NDM?

Answer 44

SCN4A gene(codes for a VGSC)

Question 45

Give examples of NDMs?

Answer 45

Potassium-aggravated myotonia (PAM), →Paramyotonia congenita (PMC) →Hyperkalemic periodic paralysis (HyperPP), →Hypokalemic periodic paralysis (HypoPP), →A form of congenital myasthenic syndrome (CMS)

Question 46

What do mutations in NDM cause?

Answer 46

→decreased rate of channel inactivation →increased rate of recovery from inactivation →slower channel deactivation

Question 47

What are some NDMs due to?

Answer 47

loss of Cl channel (CLC-1) →Less Cl channel activity →Prolonged contraction

Question 48

What does NDM result in?

Answer 48

→ paralysis

Question 49

Describe the activation of VGSC?

Answer 49

→When the membrane potential depolarises the voltage sensor domains move out of the plain of the membrane →allows sodium ions to pass through the pore →sodium flow is brief because a few ms later the so called inactivation 'lid' part of the channel then moves to and blocks the channel pore →no flow of sodium but the voltage sensors are still poking up so the channel is not closed but is INACTIVATED

Question 50

Describe VGSCs

Answer 50

→formed from one large protein comprised of 4 repeated regions and each has 6 transmembrane domains →4th transmembrane domain of each region is packed with positively charged amino acids and is known as the voltage sensor.

Question 51

How are VGSCs implicated in NDMs?

Answer 51

mutations to the gene that affects the property of inactivation will allow for longer / more persistent sodium influx.