Muscle and Contractile proteins (BAKER) Flashcards
1
Q
There are many myosin types with similiar (blank) but with differences in (blank) which correspond to differences in cargo and regulation.
A
motor domains
tails
2
Q
Why type of myosin is associated with muscle myopathies?
A
type II
3
Q
What type of myosin is associated with griscelli syndrome?
A
type V
4
Q
What type of myosin is associated with hearing loss?
A
Type VI and VII
5
Q
What is the function of myosin IIa?
A
involved in cell division
6
Q
What is the function of myosin V?
A
involved in melanosome transport and certain neurological function
7
Q
What is Griscellis syndrome and what causes it?
A
myosin Va point mtation leads to hypopigmentatiosn and neurological defects
8
Q
What is the function of myosin VI and myosin VII and what is the disease associated with this?
A
maintains organization of actin-filled stereocilia
Mutations to myosin VI and VII associated with hearing loss. and usher syndrome (VII)
9
Q
What is the structure of myosin II?
A
it is a dimer with motor domains and tails associated with heavy chains and 2 light chains (essential and regulatory)
with an active site and actin binding site
10
Q
What is essential for myosin function?
A
coordination b/w actin binding site and active site
11
Q
To generate ATP you need (blank) site.
A
actin binding site
12
Q
all myosins are (blank) motors
A
actin-based motors
13
Q
all but (blank) are plus-end directed myosin.
A
myosin VI
14
Q
Actin is a long polymer structure, the polymer is (blank) allowing for directional muscle contraction.
A
polar
15
Q
What are the sources of ATP in muscle and tell me the order that they are utilized.
A
ATP> creatinine>glycogen> lipolysis
16
Q
with anaerobic respiration what do you get?
A
lactic acid and 2 ATPs
17
Q
With aerobic respiration what do you get?
A
36 ATPs, CO2 and water and has myoglobin stores for oxygen
18
Q
Why are aerobic cells red and what surrounds them?
A
aerobic cuz of myoglobin
vascularization surrounds it
19
Q
Explain how muscle contraction works with actin and myosin
A
myosin is locked on actin in rigor configuration-> ATP binds and causes conformation on actin binding site->head displaces-> hydrolysis of ATP-> myosin binds to new site on actin filament-> release of phosphate-> power stroke and loss of ADP-> back to rigor state
20
Q
Which has a bigger lever arm, myosin II or myosin V?
A
myosin V?
21
Q
What is the mechanism of movement (working step) of actin and myosin?
A
lever arm otation
22
Q
(blank) is a high (greater than 50%) duty ratio “processive” motor. i.e one head (motor) must be bound for 50% of its ATPase cycle
A
myosin V
23
Q
(blank) transports vesicles in cells
A
myosin V
24
Q
(blank) is a low duty ratio (less than 10%) motor
A
myosin II
25
What is this:
long neck (6IQ)
organelle motor
functional unit: two heads
myosin V
26
What is this:
shot neck (2IQ)
drives muscle contraction
functional unit: ~20 heads
myosin II
27
(blank) are far from processive
muscle myosin
28
How come some myosins can be processive and others cant/
the duty ratio tells us how long a myosin can hang onto an actin and if you have a very short duty ratio, then the myosin will just fall off and you cant processively (move like monkey bars).
29
How does muscle myosin (myosin II) contract?
by forming a thick filament with about 20 muscle heads and creates a successive contraction on actin
30
Many (blank) molecules are required to propel actin filament
myosin II molecules
31
In muscle, myosin II molecules are assembled into a (blank)
thick filament
32
(blank) form by association of hydrophobic regions in the tail.
filaments
33
(blank) is the fundamental contractile unit in muscle.
muscle sarcomere
34
The (blank) contracts when myosin thick filaments and actin thin filaments slide past each other.
sarcomere
35
(blank) and (blank)cap ends o actin to keep filament length constant.
CapZ and tropomodulin
36
(blank) contains alpha-actinin an other proteins that stably join sarcomeres.
Z disc
37
(blank) maintains thick filament position in the sarcomere.
Titin
38
(blank) sets the length of the thin filament
nebulin
39
What are the two types of muscle regulation?
```
thin filament (skeletal and cardiac)
thick filament (smooth muscle)
```
40
Explain smooth muscle regulation?
phosphorylation= contraction
41
What activates myosin light chain kinase?
calcium-calmodulin
42
(blank) wraps around actin filaments blocking myosin binding sites on actin.
tropomyosin
43
(blank) binding to troponin C results in tropomyosin movement away from myosin binding sites.
calcium
44
The more calcium you add to the muscle, the more calcium that is bound to (blank) creating large powerstrokes.
troponin
45
When looking at a graph of force and calcium, what does it tell us about the behavior of calcium in contraction?
it exhibits cooperativity
46
Besides calcium, what else exhibits cooperativity?
myosin binding cuz it pushes troponin out of the way for the next myosin to attach
47
What are 5 factors that affect muscles ability to generate force and to contract?
```
myosin isoforms
frequency of stimulation
number of motor units stimulated
degree of stretch (frank-starling)
whether muscle is allowed to shorten (Force-velocity relationship)
```
48
A complete muscle twitch is divided into what three phases?
latent, contraction, relaxation
49
What is the latent period due to? So what does this mean?
AP, calcium
| There is a delay between applied voltage and increase in tension
50
What happens if you have a smaller time interval between contractions?
your second contraction will be bigger due to temporal summation of tensions
51
What happens if you have continuous stimulation of a muscle?
temporal summation (as we apply more voltage, we get more stimulation, more release of calcium, stronger contraction), then we get tetanus (generating max force) and then fatigue (decreased tension)
52
Asynchronous motor unit activity maintains a nearly (blank) in the total muscle
constant tension
53
A motor neuron and all of the muscle cells it stimulated is called a (blank)
motor unit
54
If we activate more than one motor neuron via an interneuron, what will our force be like?
increased due to recruitment
55
The strength of a muscle contraction is determined not only by the frequency of stimulation but also by the (blank and blank) of motor units recruited
number and size
56
In vivo, the number of motor units that are recruited is determined by the number of (blank) that are stimulated by the central nervous system
motor neurons
57
In addition to the frequency of stimulation and number of motor units recruited, the strength of a muscle contraction can also be altered by changing the starting length of a muscle. This is called the (blank)
length-tension relationship
58
How do you get the best contraction?
perfect overlap
59
What happens if you overstretch?
you will have little overlap and a small force
60
What happens if you have too little stretch?
you will be crowded and generate a weak force
61
What is an isometric muscle contraction?
keep muscle the same length and generate a force
62
What is an isotonic contraction?
constant force and apply tension, measure shortening and graph.
63
What will the slope of an isotonic contraction give you?
velocity of shortening
64
The heavier the load the (blank) the shortening velocity
smaller
65
(blank) make up 10-15% of the protein in the body
myosins
66
WHen you have a mutation in myosin you get a (blank)
muscle disorder
67
What happens if you have a mutation in MyHC IIa (MYHC2)?
muscle myopathy
68
What are the clinical features of muscle myopathy?
muscle weakness, atrophy near shoulders, back, hand and thigh musles.
69
What is the pathogenesis of MyHC IIa (MYHC2)?
mutations primarily to SH1 helix in myosin, thought to alter actin-myosin ATPase activity
70
What happens if you have a mutation to embryonic MyHC (MYH3)?
distal arthrogryposis. Freeman-Sheldon Syndrome, Sheldon-Hall syndrome
71
What are the clinical features Freeman-sheldon syndrome etc.?
joint contractures with predominant distal involvement
72
What is the pathogenesis of freeman-sheldon syndrome?
mutations in troponin I, troponin T, tropomyosin, perinatal myosin and embyronic myosin. thought to disrupt sarcomere development
(i.e regulatory proteins)
73
What happens if you have a mutation in B-Cardiac myosin (MyHC7)?
Laing myopathy
74
What are the clinical features of Laing myopathy?
weakness of ankle dorsiflexion and "hanging big toe"
75
What is the pathogenesis of B-cardiac myosin?
mutation in LMM region of myosin. Thought to disrupt myosin filament formation or disrupt interactions with myosin binding proteins like titin
76
What are 5 factors that affect muscles ability to generate force and to contract?
```
myosin isoforms
frequency of stimulation
number of motor units stimulated
degree of stretch (frank-starling)
whether muscle is allowed to shorten (Force-velocity relationship)
```
77
A complete muscle twitch is divided into what three phases?
latent, contraction, relaxation
78
What is the latent period due to? So what does this mean?
AP, calcium
| There is a delay between applied voltage and increase in tension
79
What happens if you have a smaller time interval between contractions?
your second contraction will be bigger due to temporal summation of tensions
80
What happens if you have continuous stimulation of a muscle?
temporal summation (as we apply more voltage, we get more stimulation, more release of calcium, stronger contraction), then we get tetanus (generating max force) and then fatigue (decreased tension)
81
Asynchronous motor unit activity maintains a nearly (blank) in the total muscle
constant tension
82
A motor neuron and all of the muscle cells it stimulated is called a (blank)
motor unit
83
If we activate more than one motor neuron via an interneuron, what will our force be like?
increased due to recruitment
84
The strength of a muscle contraction is determined not only by the frequency of stimulation but also by the (blank and blank) of motor units recruited
number and size
85
In vivo, the number of motor units that are recruited is determined by the number of (blank) that are stimulated by the central nervous system
motor neurons
86
In addition to the frequency of stimulation and number of motor units recruited, the strength of a muscle contraction can also be altered by changing the starting length of a muscle. This is called the (blank)
length-tension relationship
87
How do you get the best contraction?
perfect overlap
88
What happens if you overstretch?
you will have little overlap and a small force
89
What happens if you have too little stretch?
you will be crowded and generate a weak force
90
What is an isometric muscle contraction?
keep muscle the same length and generate a force
91
What is an isotonic contraction?
constant force and apply tension, measure shortening and graph.
92
What will the slope of an isotonic contraction give you?
velocity of shortening
93
The heavier the load the (blank) the shortening velocity
smaller
94
(blank) make up 10-15% of the protein in the body
myosins
95
WHen you have a mutation in myosin you get a (blank)
muscle disorder
96
What happens if you have a mutation in MyHC IIa (MYHC2)?
muscle myopathy
97
What are the clinical features of muscle myopathy?
muscle weakness, atrophy near shoulders, back, hand and thigh musles.
98
What is the pathogenesis of MyHC IIa (MYHC2)?
mutations primarily to SH1 helix in myosin, thought to alter actin-myosin ATPase activity
99
What happens if you have a mutation to embryonic MyHC (MYH3)?
distal arthrogryposis. Freeman-Sheldon Syndrome, Sheldon-Hall syndrome
100
What are the clinical features Freeman-sheldon syndrome etc.?
joint contractures with predominant distal involvement
101
What is the pathogenesis of freeman-sheldon syndrome?
mutations in troponin I, troponin T, tropomyosin, perinatal myosin and embyronic myosin. thought to disrupt sarcomere development
(i.e regulatory proteins)
102
What happens if you have a mutation in B-Cardiac myosin (MyHC7)?
Laing myopathy
103
What are the clinical features of Laing myopathy?
weakness of ankle dorsiflexion and "hanging big toe"
104
What is the pathogenesis of B-cardiac myosin?
mutation in LMM region of myosin. Thought to disrupt myosin filament formation or disrupt interactions with myosin binding proteins like titin
105
Point mutations to B-cardiac myosin, actin, troponin, and tropomyosin have been linked to (blank) and (Blank)
FHC (familial hypertrophic cardiomyopathy)
| DCM (dilated cardiomyopathy)
106
Myosin mutations cause (blank) and sudden death
familial hypertrophic cardiomyopathy
107
FHC mutations (blank) myosin force generation
enhance
108
DCM mutation (blank) myosin force generation
decrease
