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Molecules to Medicine IV > Muscle > Flashcards

Flashcards in Muscle Deck (71)
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1
Q

What are skeletal muscle cells called?

A

myofibers

- long and cylindrical

2
Q

What are the dimensions of a typical myofiber?

A

50-100 micro meters in diamter

up to several cm long (2.5!)

3
Q

How many nuclei do skeletal muscle cells have?

A

Up to hundreds

  • too large to be controlled by a single nucleus
  • nuclei may express different proteins depending on physical location (i.e. near motor neuron junction, near tendon)
  • on periphery -> only central after injury
4
Q

Describe typical cardiac muscle cell

A

single nucelus
shorter
small diameter

5
Q

What is one distinguishing feature of cardiac muscle?

A

intercalated discs

6
Q

What are the two functions of intercalated discs?

A
  1. physically links adjacent cells

2. contain gap junctions

7
Q

What are gap junctions?

A

transmit electrical current

- necessary for synchronous cardiac contraction

8
Q

Describe smooth muscle cells

A
2-5 micrometer diameter
spindle shapes 
central nucleus 
not striated
use same proteins to contract - different regulation
9
Q

What are myofilaments?

A

actin and myosin complex

10
Q

What are myofibrils?

A

bundle of skeletal muscle cells

11
Q

What are myofibers?

A

single muscle cell

12
Q

What are myocytes?

A

cardiac muscle cells

13
Q

How is the unit of one sarcomere defined?

A

from 1 z line to the next z line

14
Q

How is the sarcoplasmic reticulum related to myofibrils?

A

each myofibril is covers with its own sarcoplasmic reticulum

15
Q

What protein forms the thin filament?

A

actin

16
Q

What is the structure of actin in skeletal muscles?

A

F-actin (filamentous - v. globular)
double stranded
helical (intertwined strings of pearls)
1 micrometer long

17
Q

What are the regulatory proteins bound to actin?

A

Tropomyosin

Troponin

18
Q

How are tropomyosin and troponin bound to actin?

A
Tropomyosin
- rod
- binds length of 6-7 actin
Troponin
- bound to one end of tropomyosin (I,T, & C subunits)
19
Q

What protein forms the thick filament?

A

Myosin

20
Q

What is the structure of myosin?

A

6 proteins (3 pairs)

  • 1 pair heavy
  • 2 pair light

Each heavy chain has globular head

Pairs of heads staggered along length and around circumference of filament

1.6 micrometers long

21
Q

How do tropomyosin and troponin control actin-myosin binding?

A

At Rest:
tropomyosin covers actin binding site

As Ca2+ levels rise:
troponin binds Ca2+
->induces conformation change in tropomyosin (they are bound together) -> actin binding site exposed

22
Q

How does the myosin head bind to actin?

A

Once actin binding site is exposed “spring loaded” myosin binds - releases Energy on binding
=> immediately exerts 5pN force and shortens sarcomere by 8nm

23
Q

How does myosin dissociate from actin?

A

Myosin remains bound to actin until ATP binds to myosin

- binding allows dissociation -> returns myosin to high energy state ready to bind actin again

24
Q

How do muscles contract if each myosin-actin power stroke is only 8nm?

A
  1. sarcomeres contracting in series summate linerally ( can be hundreds to thousands)
  2. many myosin-actin cycles occur during each contraction
25
Q

How quickly can a fast twitch myofiber contract?

A

20 times/sec

26
Q

How quickly can a slow twitch myofiber contract?

A

5 times/sec

27
Q

How is smooth muscle regulated?

A

No troponin
Calcium key regulator
Ca binds calmodulin -> binds CaM Kinase -> phosphorylates a light chain of myosin

Phosphorylated myosin binds to actin => generates force

28
Q

How does smooth muscle contraction differ from skeletal and cardiac muscle contraction?

A

slower (up to 1 sec to generate full force)
Ca removed by pumps and Na-Ca exchangers
Kinases inactivated by removal of Ca

smooth muscle can remain in locked state-> contracting with myosin bound to ATP without consuming ATP
THINK OF THE SPHINCTERS!!!

29
Q

What is the normal function of dystrophin?

A

One of the largest proteins
Links cytoplasm with extracellular matrix
- associates with globular actin (g-actin) beneath plasma membrane and with surface membrane
- Part of a protein complex
- Binds extracellular matrix molecules like laminin

30
Q

What are 3 other important structural proteins?

A

Titin
Nebulin
Alpha-actinin

31
Q

What is the function of Titin?

A
Links myosin thick filaments to Z-line
=> keeps myosin centered in sarcomere
- large
- myosin bound side inflexible
- z line bound side extensible
- contribute to passive tension in muscle
32
Q

What is the function of nebulin?

A

Keeps thin filaments of actin organized

  • large
  • contribute to passive tension in muscle
33
Q

What is the function of the alpha-actinin?

A

cross-links actin at the Z-line

34
Q

What are the causes of familial cardiacmyopathy?

A

Single amino acid mutations

  • in myosin heavy chain at head group (where it binds actin and where binds ATP)
  • in troponin

Thicker left ventricle wall

35
Q

How many places is each skeletal muscle innervated?

A

ONCE

exception: extra ocular muscles

36
Q

Describe the action potential leading to the contraction of a skeletal muscle

A

Action potential in motor axon -> neurotransmitter ACh released -> ACh diffuses across synaptic cleft & binds AChR -> ion channel opens -> depolarization -> Na channels open

Propagates in both directions only takes 1-5ms
Contraction takes 50-100ms

37
Q

What is the source of Ca2+ in skeletal muscle?

A

Sarcoplasmic reticulum

38
Q

How is Ca2+ released from the SR?

A

AP transmitted by transverse tubule (t-tubule) -[Huxley and Taylor] ->
NO ELECTRICAL CONTINUITY HERE
(not enough charge to change capacitance)
-> AP is somehow translated from t-tubules to SR as induces Ca release

ECITATION-CONTRACTION COUPLING

39
Q

What is the location where the SR contacts the t-tubule called?

A

terminal cisterna

Also: triad- electron dense - dark in EM proteins

40
Q

Where is calsequestrin locatated? and what is its function?

A

in terminal cisterna

binds ~50 Ca++ each

41
Q

What is the current theory on how the AP in the t-tubule is translated to Ca++ release in the SR?

A

DHPR (membrane protein complex on t-tubules) has voltage gated Ca++ channel
RyR releases Ca++ from SR
Depolarization -> conformational change in DHPR -> Ca++ release opens-> Ca++ out of SR

42
Q

What can induce malignant hyperthermia?

A
Potent & Volatile anesthetics
- halothane
- succinylcholine
=> steady Ca++ leak activates Ca ATP pump
- futile
- heat producing 
- lethal
43
Q

What are symptoms of malignant hyperthermia?

A
  • rapid temperature rise -> >1/ 5 min
  • muscle rigidity - masseter spasm
  • Increase CO2 production
  • Rhabidomyolysis (muscle breakdown)
  • Hyperthermia
44
Q

What drug can be used to reverse malignant hyperthermia?

A

Dantrolene -> block Ca++ release from SR

45
Q

Why can skeletal muscles work, but not cardiac or vise versa?

A

Many genes code for same proteins

- isoforms

46
Q

What terminates the myosin-actin interaction in muscle contraction?

A

Ca ATPase pump puts Ca++ back into SR -> cytoplasmic Ca returns to low level (<0.1micromolar)

47
Q

Why is the t-tubule system necessary?

A

myofibrils are too large for the AP to diffuse through efficiently -> MUST have conduction system (50-100micrometers)

48
Q

How is excitation-contraction coupling completed in cardiac muscle?

A

Ca must bind Ca-release channel - otherwise identical to skeletal muscle

49
Q

How is excitation-contraction coupling completed in smooth muscle?

A

no need for t-tubules (1-2 micrometer diameter)

- do have some SR

50
Q

How are tension and actin-myosin overlap related?

A

0 overlap = 0 tension
tension increases linearly with overlap
UNTIL
actin reaches central region of thick fillaments
-> 0 myosin head groups => plateaus
OR
if actin fillaments interdigitate in middle of sarcomere -> tension decreases

51
Q

What is a motor unit?

A

muscle fibers innervated by a motor neuron

- each time neuron fires action potential - fibers innervated by neuron contract in unison

52
Q

How many muscle fibers do each motor neuron innervate?

A

RANGE
3 in extra occular
10-20 in fine motor
100s in large muscles
total number of motor units in muscle = total number of muscle fibers
(each motor fiber innervated by ONLY ONE motor neuron)

53
Q

How do motor units relate to the strength of contration?

A

more motor units -> more strength

54
Q

How does the innervation of cardia and smooth muscle differ from the innervation of skeletal muscle?

A

innervated
BUT
innate excitability
- excitatory and inhibitory innervation modulate

linked by gap junctions (electrically coupled)

55
Q

What are the types of muscle fibers?

A

slow
fast
intermediate

56
Q

How do the muscle fiber types differ?

A

proportion of mitochondria
amount of oxidative enzymes
resistance to fatigue
speed of contraction

57
Q

How many types of fibers are in a motor unit?

A

ONLY ONE

homogeneous

58
Q

What 3 factors can grade tension in skeletal muscles?

A
  1. increased frequency of action potentials
  2. recruitment of additional motor units
  3. changing length of muscle (minor)
59
Q

How is tension graded in cardiac and smooth muscle?

A
  1. neurotransmitters and hormone-like molecules

2. LENGTH - not fixed by attachements to bone

60
Q

What are the stem cells for muscles? What is their function?

A

satellite cells

- source of new myoblasts to repair injury

61
Q

How are satellite cells related to Duchene Muscular Dystrophy?

A

skeletal muscle cells weakened or damaged by absence of dystrophin
- satellite cells continuously repairing
=> depleted/ loose ability to keep up with degeneration

62
Q

How does cardiac muscle repair itself?

A

0 satellite cells

- little or no repair after MI

63
Q

How do smooth muscles repair themselves?

A

dedifferntiate -> divide -> regenerate/ redifferendiate!

  • contribute to smooth muscle tumors?
  • can occur anywhere!
64
Q

When skeletal muscles get bigger, do the fibers grow, or are more fibers added?

A

already existent fibers grow

  • have a set number of fibers
  • grow or decline/ atrophy
65
Q

What are the 4 major causes of muscle fatigue?

A
  1. ineffective propagation of AP in t-tubule (K build up, Na reduction)
  2. decreased or 0 release of Ca++ from SR
  3. decreased Ca++ affinity to troponin
  4. decreased force generated by myofilaments
66
Q

What smooth muscles have action potentials?

A

longitudinal muscles of gut
uterus
bladder
(Ca++ not Na+ APs)

67
Q

What are some of the cellular consequences of HCM?

A

interstitial fibrosis

dyplastic intramyocardial arterioles (disorganized sarcomeres-> ischemia - harder for aa to get blood there)

68
Q

What are some phenotypes of HCM?

A

often asymptomatic!!!!
- some dyspena, angina, syncope

  • cardiac murmur (LV outflow obstruction)
  • Arythmias -> syncope/ sudden death
69
Q

How is HCM diagnosed?

A

EKG, echo, genetic screeen

70
Q

What is myostatin?

A

inhibitor of muscle growth

71
Q

What are some current treatments of muscular dystrophy?

A

Symptomatic

  • supportive
  • leg braces
  • surgical tendon release (rigidity- toe walking)
  • CPAP
  • Cortico steroids (side effects)
  • Ambulatory assistance devices
  • multidiciplinary care

Disease targeted

  • Growth modulating agents (myostatin)
  • Anti inflammatory - 2nd messenger modulators
  • antisense oligonucliotieds (ASO) with EXON SKIPPING capacity ( skip incorrect stop codon)
  • Supress stop codon
  • Myoblasts/ stem cells