Lecture 11 - Diseases of the nerve and motor units

Question 1

What are the three major types of muscle?

Answer 1

1. smooth
2. skeletal
3. cardiac

Question 1

What are the three ways neurological disorder affect movement?

Answer 1

1. AP conduction along MN
2. synaptic transmission from MN to muscle
3. Muscle contraction itself

Question 2

What four parts of the NMj can be affected?

Answer 2

1. cell body of MN - MN disease
2. axon of MN - peripheral neuropathy
3. NMJ synapse - disorder of NMJ
4. muscle fiber - myopathy

Question 3

What two MN disease where the cell body of the MN is affected were discussed in class?

Answer 3

ALS - can cause pain in extremetiris and muscle to weaken and voice to squeak and freezing - die due to airway death
SMA - found in children born with it

Question 4

What are the two gene associated with ALS?

Answer 4

1. sod1 - scavegnes free radical and prevent oxidative stress and is enzyme in mitochondria
2. C9orf72 - GGGGCC expansion causes cytotoxicity causes defects in nuclear pore complex - expansion can cause haploinsufficency - or mRNA toxivity or protein toxivity

Question 5

What gene is associated in SMA?

Answer 5

SMN1 gene - defective rna splicing and processing
-can inject dsRNA of smn2 to make it more stable so it can do the splicing more

Question 6

What happened in the SMN mutated mice?

Answer 6

could not breathe or move

Question 7

What two things can cause a peripheral neuropathy in which the axon of the MN is affected?

Answer 7

1. impair in myelination of MN - schwann cell cannot myelinate
2. imapir axonal function itself

Question 8

Apply a shock at S1 or S2 and the longer the latency what happens? - this means the slower the conduction along the peripoherla nerve which indicates peripheral pathiology in the axon myelin

Question 9

Would have deynshronzied aps if have issue with myelination

Question 10

What can giver rise to peripheral demyleination?

Answer 10

defects in multiple gene - Tfs, ABC transporter in peroxisomes, genes involved in organizing myelin

Question 11

How are peripheral axons wrapped in myelin?

Answer 11

so that the axon is compact and tight except near the nodes of ranvier

Question 12

What defines major dense lines of myelin?

Answer 12

rings of cytoplasm that have myelin basic protein

Question 13

What are the three myelin associated proteins that are defective in 3 different demyelinating neuropathies?

Answer 13

P0, PMP22, connexin-32

Question 14

How do genetic defects in intracellualr neuronal proteins cause axonal neuropatheis?

Answer 14

stress to axonal cytoskleeton and axonal transport can be a major trigger for this - i.e. not enough sodium channels can cause not as great an AP via transport defects

Question 15

What is the NMJ synaptic disease discussed in class?

Answer 15

myasthenia gravis

Question 16

What happens in myasthenia gravis?

Answer 16

the immune system attacks postsyanptic achr leading to reduces achrs and simplified synaptic folds

Question 17

If you inject an acetylcholineetserase inhibitor like neostigmine what happens?

Answer 17

myasthenia gravis is better cause more ach in terminal

Question 18

How does the turnoves of achrs increase in MG?

Answer 18

cause of crosslinkong of asntibodies which cayses endocytosis and destruction of receptotrs and the membrane to lysis

Question 19

What are the two myopathies discussed in class?

Answer 19

1. muscular dystrophy
2. myotonia

Question 20

What happens in muscular dystrophy?

Answer 20

defective protein weakens the muscle membane or slow repair after injury mutation in dystrophin gene in which scaffold that stabilizes structural complexes in muscles

Question 21

What does dystrophin do?

Answer 21

anchors muscle to ecm and is a scaffold protein

Question 22

What happens in severe duchenne dystrophy?

Answer 22

deletion of on exon causes stopn codon and severe truncation of gene

Question 23

What happens in Becker or mild dystrophy?

Answer 23

four exons removed causing a functional but removed segment of protein

Question 24

What causes myotonia?

Answer 24

impaired inactuvation in sodium channels - no ball longer chain - rapid burst of ap from a single stimulus

Question 25

What can cause myotoniab or muscle paralysis?

Answer 25

spectrum of voltage gated ion channel channelopathies can cause this

Question 26

What happens when MNs are diseased?

Answer 26

muscles formerly innervated by cell A become atrophic and adjacent neyron then hyperinnervates them leading to a larger reponse in slight contaction but lower maximal contraction
-frequecny decrease and amplitude increase - cause less muscles are innervated but dome muscle are hyperinnervated so get a huge spike

Question 27

What happens when the muscle is diseased?

Answer 27

the number of muscle fibers in each motor unit are reduced some shrink and become nonfunctional so the maximal response is reduces and smaller and shirter in duration - same frequecny less amplitude cause less are firing