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1
Q

The outer membrane of mitochondria is _____

A

semi-permeable

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2
Q

Mitochondrial membranes are transported via ____ and ____ complexes

A

TOM and TIM

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3
Q

GTPases involved in fusion

A

Mfn OPA1

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4
Q

GTPases involved in fission

A

Fis1 and DRP

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5
Q

Free energy released in oxidation of glucose

A

NADH

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6
Q

Electrons transferred from NADH to ___ to form ____

A

O2 to form H2O

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7
Q

Two parts of ATP synthase

A

f1 and F0

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8
Q

F0 spans the ______ mitochondria membrane and forms a ______

A

inner

proton channel

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9
Q

F1 is bound to ___ and ____

A

F0

is an actual enzyme that makes ATP

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10
Q

Once made, ATP is transported out of mitochondria via___

A

ATP-ADP antiporter

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11
Q

Ischemic injury results in ____________ permeabilization of inner and outer mitochondria membranes, resulting in cytochrome release and elimination of proton gradient

A

MPTP dependent

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12
Q

Damaged mitochondria make excessive amounts of ___

A

ROS

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13
Q

Mitochondria quality is strictly controlled at three levels:

A
  1. mitochondrial proteases (MAAA, iAAA, and Lon) degrade misfolded proteins
  2. fusion with healthy mitochondria can fix it
  3. apoptosis
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14
Q

Arsenic

A

inhibits oxidative phosphorylation and ATP production

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15
Q

Mfn and OPA mutations

A
  • autosomal dominant optic atrophy

- charcot- marie tooth type 2A

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16
Q

Mutation in MAAA

A

Hereditary spastic paraplegia

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17
Q

CF is caused by a defect in an

A

ATP-binding cassette transporter gene on chromosome 7 that encodes for the CF Transmembrane Conductance Regulator (CFTR) protein

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18
Q

Categorization of CFTR mutations

A

5 main classes

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19
Q

Most common mutation in CF

A

F508del

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20
Q

Major cause of morbidity and mortality in CF

A

lung involvement

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21
Q

depleted _______ layer in the lung leads to impaired ___________ and altered host defense

A

pericilliary

mucocilliary clearance

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22
Q

CF- Sinus

A

chronic sinus infections, nasal polyps

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23
Q

CF- lung

A

respiratory inections, bronchiectasis

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24
Q

CF- pancreas-

A

exocrine pancreatic insufficiency

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25
Q

CF- GI

A

Distal ileal obstructive syndrome

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26
Q

Sweat chloride >___ mmol/L indicative of CF

A

60

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27
Q

Diagnosing CF

A 
IRT/IRT/DNA
immunoreactive trysinogen (pancreatic enzyme)
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28
Q

Nutrition treatment CF

A

HIgh- calorie, protein, fat

Supplementation of vitamins A, D, E, and K (fat soluble)

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29
Q

Lung treatment CF

A

airway clearance therapy
antibiotic therapy targetinf common CF related bacteria
Anti-inflammatory treatments

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30
Q

CFTR modulators

A

Target specific CFTR mutations

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31
Q

Mutation treated with Ivacaftor

A

G551D

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32
Q

Orkambi mutation

A

F508del

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33
Q

Median life expectancy CF

A

40

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34
Q

Basal bodies are ____

A

Microtubule rich cylinder shaped structures

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35
Q

Basal bodies are made of

A

9 triplet microtubules (A-B-C tubules)

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36
Q

Distal end of basal bodies responsible for

A

nucleating the cilium

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37
Q

Structural skeleton of cilium

A

Axoneme

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38
Q

Structure of axoneme

A

A-B tubules that form from a ans b tubules of basal body

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39
Q

function of axoneme

A

scaffolding

tracks for movement within cilia

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40
Q

Linker of basal body to axonome and ciliary body

A

transition zone

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41
Q

“Gatekeeping” function of transition zone

A

limits diffusion of membrane and soluble proteins into and out of cilium

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42
Q

Part of cilia continuous with the cellular plasma membrane

A

ciliary membrane

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43
Q

mechanism of transport of signaling components within cilia

A

intragflagellar transport

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44
Q

proteins involved in movement to ciliary tip

A

Kinesin-2

IFT-B

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45
Q

Ciliary retrograde transport proteins

A

dynein 2

IFT-A

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46
Q

Two phases of ciliogenesis

A
  1. centrioles/basal bodies assembled

2. Formation of cilium

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47
Q

Basal bodies are derived from

A

centrioles

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48
Q

Centriole that functions as basal body

A

Mother centriole

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49
Q

Ciliogenesis occurs during _____ of the cell cycle

A

G1 (or G0)

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50
Q

Ciliogenesis begins when the distal end of a basal body is capped by a _____

A

ciliary vesicle

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51
Q

What happens after a basal body is capped by a ciliary vesicle?

A

Microtubule doublets then assemble into the ciliary vesicle before the entire structure fuses with the plasma membrane of the cell

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52
Q

Motile cilia are required for the movement of fluid in the ____, _____, and _____ tracts

A

respiratory, neural, and reproductive

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53
Q

Motility of motile cilia is produced by ____

A

axonemal dynein dependent sliding motion between the doublet microtubules of the ciliary axoneme

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54
Q

Motile cilia microtubule arrangement

A

9+2

Not all have this arrangement (Nodal)

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55
Q

The distinguishing factor between motile and immotile cilia is the presence of

A

axonemal dynein arms between the doublet microtubules

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56
Q

Non-motile, sensory or primary cilia microtubule arrangement

A

9 + 0

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57
Q

Pathway well established to signal through cilia

A

Hedgehog (Hh)

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58
Q

Hh target

A

Gli transcriptional activator

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59
Q

Downstream targets of Hh signaling

A

limb formation
bone formation and homeostasis
neurogenesis

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60
Q

Characteristics of ciliopathies (6)

A
  1. rare
  2. pleiotropic
  3. Overlapping
  4. structural
  5. diverse
  6. genetically complex
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61
Q

Two examples of ciliopathies

A
  1. Bardet- biedi syndrome (BBS)

2. Polycystic kidney disease (PKD)

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62
Q

BBS is autosomal ____

A

recessive

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63
Q

BBS proteins participate in a protein complex that is required for

A

vesicle transport within the cilium

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64
Q

Symptoms of BBS

A 
Photoreceptor degeneration  
• Anosmia 
• Mental retardation / Developmental delay 
• Neural tube defects 
• Obesity 
• Hypogonadism 
• Kidney defects 
• Polydactyly 
• Diabetes
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65
Q

PKD is autosomal ____

A

dominant (ADPKD) and recessive (ARPKD)

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66
Q

ARKPD is caused by _____ mutations

A

fibrocystin

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67
Q

ADKPD is caused by mutations in ____ and _____

A

polycistin 1 and polycistin 2

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68
Q

PKD genes encode

A

channel proteins responsible for calcium signaling

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69
Q

Symptoms of PKD

A

Renal cysts
• Liver and pancreas cysts
• Intracranial aneurysms

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70
Q

Epithelial tissues are a-

A

avascular

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71
Q

Functions of epithelia (7)

A
  1. Barrier
  2. selective absorption and transport
  3. secretion
  4. Movement of particles
  5. Biochemical modification of molecules
  6. Communication
  7. Reception of sensory stimuli
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72
Q

Tissue that faces blood/lymph

A

endothelium

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73
Q

sheets of cells that line the enclosed internal spaces of the body cavities are called

A

mesothelium

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74
Q

____ layer of all mucosa is epithelium

A

Surface

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75
Q

Examples of organized comprised of epithelial cells that are the primary functional units

A

liver, pancreas, kidney

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76
Q

Epithelia are derived from which germ layers>

A

All three

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77
Q

Two layers of mucosae

A
  1. outer epithelium

2. CT underneath- lamina propia

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78
Q

Lamina propia contain a lot of ____

A

immune system cells and small blood vessels

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79
Q

Below lamina propia

A

submucosa

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80
Q

Simple epithelia

A

have all cells arranged in a single layer or sheet

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81
Q

Stratified epithelia

A

have more than one layer of cells in which cells of the outer layers do not directly contact the basal lamina.

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82
Q

-Pseudostratified epithelia

A

are a special case where some cells do not reach the free surface (giving a stratified appearance), but all directly rest on the basal lamina

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83
Q

-Squamous cells

A

e flattened cells

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84
Q

-Transitional epithelia

A

(found around the bladder) are a special case: these epithelia are stratified, but when stretched change their shape from cuboidal to squamous, and appear to decrease the layering: this is indicative of a tightly adherent epithelium that is very resilient and stretchable

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85
Q

Key core proteins of tight junctions

A

occludins and claudins

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86
Q

Adherence junctions contain specific ___ that link to ___ filaments

A

Cadherins

actin filaments and other signaling proteins

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87
Q

Desmosomes

A

Promote mechanical strength and resist shearing forces and promote the structural organization of the epithelial sheet

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88
Q

Core components of desmosomes

A

Cadherins that link to intermediate filaments

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89
Q

Key aspects of epithelial polarity

A
  1. plasma membrane composition is locally separated into domains
  2. Cytoplasm is polarized
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90
Q

endocytosis of substances from one membrane region, followed by trans-cellular transport of the vesicles and their exocytosis from another membrane region

A

transcytosis

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91
Q

Apical surface modifications

A
  1. microvilli

2. cilia

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92
Q

Unusual type of microvillus found in epididymis and sensory cells in ear

A

stereocilia- not related to cilia

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93
Q

microvilli contain ___, while cilia contain ____

A

actin

microtubules

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94
Q

Basal laminae are formed by a special type of network- forming ____

A

collagen

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95
Q

Glycoproteins common to basal laminae

A

laminins and enactin

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96
Q

Important functions of basal laminae

A
  1. They mediate attachment of epithelia to the underlying connective tissue.
  2. Basal laminae often contribute to selective filtration of substances diffusing to or from the epithelia.
  3. They are necessary for the establishment and maintenance of epithelial cell polarity.
  4. They can serve as specific “highways” for the migration of cells through connective tissue.
  5. They provide a barrier to movement of invading microbes or cancerous cell into other tissues.
  6. They control the gene expression of cells to affect their proliferation or development.
  7. They control the development, morphogenesis, and organization of epithelial cells, providing a sort of “tissue scaffolding” function. Thus, they are critical to the repair of epithelial tissue following damage by injury or disease.
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97
Q

Epithelial cells directly connect to basal laminae by attachment of

A

hemidesmosomes and focal adhesions on the basal surface of epithelial cell to components of the basal lamina

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98
Q

for connections between basal surface and basal lamina

A

integrins

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99
Q

Different integrins of focal adhesions connect to ____ inside the epithelial cell

A

Actin filaments

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100
Q

Most, if not all epithelia contain stem cells that

A

(i) are competent for cell division, (ii) self renew: regeneration of a “mother” stem cell with each division, and (iii) produce differentiated cell types specific to each epithelia.

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101
Q

Stem cell daughters that proliferate themselves

A

transit amplifying cells

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102
Q

A specific stem cell type, its intermediate progeny, and their differentiated progeny are collectively called

A

cell lineage

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103
Q

Tarceva (erlotinib)

A

inactivates the EGF receptor and is commonly used to treat lung and pancreatic cancers).

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104
Q

Two major types of epithelial glands

A
  1. exocrine

2. endocrine

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105
Q

Exocrine secrete on the ___ side

A

apical

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106
Q

Two ways glands secrete

A
  1. exocytosis (merocrine or apocrine glands)

2. Total cell disintegration (holocrine glands, secrete entire contents)

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107
Q

Exocrine glands are typically ____

A

multicellular

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108
Q

Two main components of exocrine glands

A
  1. Secretory units

2. Ducts

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109
Q

Secretory units can be organized into bowl or flask-shaped lobules called.. Or tubes

A

Alveoli or acini

tubular

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110
Q

Ducts

A

tubular structures that emanate from the secretory units

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111
Q

Glands that possess a single duct are classified as ______ glands, whereas those with multiple branched ducts are called ______ glands.

A

Simple

Compund

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112
Q

3 general exocrine glands of body tubes

A
  1. Mucous
  2. Serous
  3. Mixed
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113
Q

During endocrine secretion, hormones must cross ____ and _____ of the wpithelium to reach the blood stream

A

basal surface

basal lamina

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114
Q

Pemphigus

A

autoimmune disease in which antibodies are produced against components of desmosomes in skin, leading to extensive blistering

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115
Q

Cancers of epithelial origin

A

carcinomas

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116
Q

Cancers derived from glandular epithelium

A

adenocarcinoma

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117
Q

Connective tissue near body surface

A

Superficial fascia

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118
Q

Function of connective tissue

A
  1. To provide mechanical strength and support for the specialized tissues of organs.
  2. To conduct and control the exchange of nutrients, metabolites, and signaling ligands
  3. To directly control the behavior and functions of cells that contact the connective tissue matrix (the ECM)
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119
Q

Two classes of cells in connective tissue

A
  1. Resident cells of the CT family

2. Immigrant blood-derived cells

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120
Q

6 examples of immigrant blood-derived cells

A
  1. lymphocytes- acquired immunity
  2. macrophages- phagocytosis
  3. neutrophils and eosinophils- bacterial defense
  4. mast cells- promote swelling
  5. Osteoclasts- bone resorption
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121
Q

Components of ECM

A

(A). Structural fibers which provide mechanical strength and resiliency. (B). A hydrated gelatinous material, called the ground substance, in which the structural fibers are enmeshed.
(C). Numerous other extracellular macromolecules embedded within or diffusing through the ECM.

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122
Q

Most abundant structural fibers of ECM

A

Collagen

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123
Q

Collagen fibers are formed from ___ intertwined polypeptides, individually called ___

A

3

alpha chain

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124
Q

3 types of collagen fibers

A
  1. Fabrillar
  2. Fibril associated
  3. Network-forming
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125
Q

Loose connective tissues contain

A

thin collagen fibrils that are relatively sparse, and are arranged in irregular lattices.

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126
Q

Dense connective tissues contain ______ that are very abundant relative to ground substance, and have a ___ number of cells.

A

thick collagen fibrils

low

127
Q

The individual polypeptides of collagen are assembled into a triple helix where?

A

Intracellularly

128
Q

Extracellular modifications of collagen

A

N and c terminals cleaved by proteases
formation of bundles
enzymes catalyze chemical cross links (increase tensile strength)

129
Q

Elastic fibers contain proteins ___ and ___

A

elastin and fibrillin

130
Q

Major components of ground substance

A
  1. Proteoglycans
  2. other secreted proteins and glycoproteins
  3. Inrganic and small organic solutes
  4. Water
131
Q

3 properties of GAGs

A
  1. Negatively charged
  2. Rigid structure allows them to form gels
  3. some can bind to ans activate/inactivate other proteins
132
Q

Events in wound healing

A
  1. Inflammation and blood clotting
  2. New tissue formation
  3. Tissue remodeling
133
Q

Signaling compounds in inflammation

A

(i) increase water permeability of capillary endothelia leading to swelling,
(ii) increase cellular permeability of endothelia, to promote migration of monocytes, lymphcytes and other blood cells into the C.T.,
(iii) attract migration of white cells to the site of the wound (chemotaxis), (iv) stimulate proliferation of fibroblasts and differentiation of monocytes into macrophages

134
Q

Histamine is secreted by

A

mast cells

135
Q

histamines promote

A

endothelial permeabilization

136
Q

Matrix of bone is ___ or ___

A

mineralized or calcified

137
Q

Bone is ____, while cartilage is much _____

A

dynamic

less dynamic

138
Q

Cartilage is ___ in its matrix

A

avascular

139
Q

two main functions of cartilage

A

1) to provide a resilient but pliable support structure. (2) to direct the formation and growth of bone

140
Q

Cartilage cells that make matrix and tissue

A

Chondroctes

141
Q

CT that surrounds cartilage

A

pericondrium

142
Q

Isolated compartment in which chondrocytes reside

A

lacuna

143
Q

Cartilage are distinguished based on differences in their ____

A

Matrix

144
Q

3 types of cartilage

A
  1. Hyaline cartilage
  2. Elastic cartilage
  3. Fibrocartilage
145
Q

Hyaline cartilage contains collagen that forms relatively____ fibrils that are generally arranged in an _______

A

thin

irregular three dimensional pattern

146
Q

Ground substance of hyaline cartilage is rich in ____ and ____

A 
proteoglycans
hyaluronic acid (promotes hydration and flexibility)
147
Q

Structural properties of Hyaline ECM

A

a. Allows metabolites to readily diffuse through the tissue.
b. Promotes resiliency to compression forces during joint movement.
c. Allows growth of chondrocytes and matrix from within the matrix.
d. During growth, it can calcify and attract cell that initiate bone formation

148
Q

Distinguishing feature of elastic cartilage from hyaline cartilage

A

elastic fibers and sheets of elastic material

149
Q

Fibrocartilage

A

large bundles of regularly arranged collagen

150
Q

Bone marrow consists of either __ or ___

A 
hematopoietic tissue (red bone marrow)
adipose cells (white bone marrow)
151
Q

The inner surface where trabeculae contact internal soft tissue is called the

A

endosteum

152
Q

Specialized cell types of bone cells

A
  1. osteoprogenitor
  2. osteoblasts
  3. osteocytes
  4. osteoclasts
153
Q

Osteoprogenitor cells

A

stem cells

154
Q

osteoblasts

A

line the inner layers of both periosteal and endosteal surfaces where bone growth or remodeling is occurri

155
Q

osteoblasts secrete un-mineralized ECM called ___

A

osteoid

156
Q

Osteoblast vesivles containing enzymes that initiate bone calcification

A

matrix vesicles

157
Q

Osteoblasts are connected by

A

gap junctions

158
Q

cells derived from oseoblasts

A

Osteocytes

159
Q

Unlike chondrocytes, osteocytes do not __

A

divide

arrest in G0

160
Q

Osteocytes extend long processes through tiny channels called ___

A

canaliculi

161
Q

Osteoclasts are derived from

A

monocytes in the blood

162
Q

Functions of osteoclasts

A

(1) they degrade cartilage or bone matrix to allow inward growth of blood vessels during bone formation (discussed below).
(2) they function to resorb already made bone to promote remodeling of the bone matrix.
(3) They resorb bone for the purpose of mobilizing Ca2+ into the bloodstream (critical for maintaining proper Ca2+ concentrations in blood).

163
Q

ECm of bone is uniques since it contains large amounts of crystallized ___ and ____

A

Ca2+

PO4 (hydroxyapatite)

164
Q

In long bones, channels that traverse the long axis through compact bone are called

A

Haversian canals

165
Q

Lammelae + haversion canal

A

osteon

166
Q

canals that link together haversian canals and the periosteum

A

Volkmann’s canals

167
Q

Two ways that bone is formed

A
  1. Intramembranous ossification

2. Endochondral ossification

168
Q

Intramembranous ossification

A

in the absence of pre-made cartilage tissue

  1. mesenchymal cells come together (condensation
  2. transform into osteoprogenitors
  3. differentiate into osteoblasts
  4. osteoblasts secrete osteoid
169
Q

Endochondral ossification

A

cartilage model

170
Q

Formation of the cartilage model

A
  1. mesenchymal cells differentiate into chondrocytes
  2. Chondrocytes secrete matrix typical of hyaline cartilage
  3. Individual chondrocytes become encased in their lacuna
  4. cartilage continues to grow
171
Q

Two different growth methods cartilage

A
  1. Appositional growth- growth at the surface

2. Intersitial growth- growth from within

172
Q

Groups of chondroctyes within a lacuna or still close together are actually clones of cells derived from mitosis and are called

A

isogenious groups

173
Q

Crucial region of continued growth in the length of the bone

A

epiphyseal plate

174
Q

Bone growth stops when proliferation of the ____ stops

A

cartilage

175
Q

Once growth stops, only a sheath of non-proliferative cartilage remains at the very end (the articular surface) of the epiphysis; this is called

A

Articular cartilage

176
Q

Growth in the diameter of bone occurs in the ___

A

periosteum

appositional growth

177
Q

In adult bone, most of the resorptive activity occurs at the ____ surface

A

endosteal

178
Q

Osteoblasts initiate mineralization of the osteoid by

A

secreting matrix vesicles

179
Q

Bone and cartilage regulation is mediated by:

A
  1. short range singals (BMPs)
  2. Long range signals from endocrine glands
  3. Mechanical stress
  4. Neuronal stimulation
180
Q

BMPs

A

trigger intracellular protein phosphorylation that alters gene expression, which in turn promotes specific patterns of differentiation

181
Q

Parathyroid hormone stimulates

A

calcium liberation

182
Q

calcitonin

A

stimulates calcium uptake

183
Q

Vitamin D important for

A

Systems that promote calcium uptake from the intestine

184
Q

Lung cancer screening

A

Low dose CT

185
Q

Lung cancer screening caused a __ reduction in cancer mortality and ___ reduction in all cause mortality

A

20%

7%

186
Q

Problem with lung cancer screening

A

False positive rates- 95%

187
Q

Subtypes of lung cancer

A

Squamous carcinoma- 30%
Adenocarcinoma- 40%
Small Cell- 15%
Large cell + other- 15%

188
Q

2 types of EGFR inhibitors

A

antibody- extracellular

Tyrosine kinase inhibitors- intracellular

189
Q

ALK mutation in lung cancer

A

ALK gene on chromosome 2 fuses with EML 4

detected with FISH

190
Q

_____ is a receptor on a T cell that can interact with the _____ receptor on a cancer cell. This interaction ____ t cell function

A

PD-1
PD-L1
inhibits

191
Q

2 PD-L1 antibodies

A

Nivolumab

Pembrolizumab

192
Q

Two types of resistance mechanisms

A

Primary- already in tumr

Acquired- developed during therapy

193
Q

aorta to capillaries:
_____ # of vessels
______ overall cross sectional diameter

A

2-3 billion fold increase in

500 fold increase in cross sectional diameter

194
Q

Blood flow is slowest in _____

A

capillaries and venules

195
Q

tunica intima made of:

A

endothelial cells

layer of elastic and loose collagenous tissues containing intimal cells (in larger vessels)

196
Q

Tunica media made of:

A

multiple layers of elastic laminae, smooth muscle cells, or collagen

197
Q

Tunica adventitia made of:

A 
Collagenous tissue
Vasa vasorum (in larger vessels)
198
Q

Smooth muscle is found in the media from the aorta to the ____

A

Arterioles

199
Q

The elastic layers are crucial to permit ____

A

l to permit expansion of the vessels after systolic contraction of the heart, dampening the systolic blood pressure

200
Q

Smooth muscle, particularly in the arterioles, permits

A

control of blood flow to capillary beds

201
Q

How many elastic layers are in the aorta

A

Typically around 30-40

202
Q

How may elastic layers in muscular arteries?

A

two well-defined

203
Q

Characteristics of smaller muscular arteries

A
  • lose outer elastic lamina
  • relatively large layer of smooth muscle
  • adventitia same width as media and merges with surrounding connective tissue
204
Q

Arteriole characteristics

A
  • inner lining of endothelial cells on a thin basement membrane
  • this is surrounded by 1-2 layers of smooth muscle cells
  • outer collagenous tissue which blends with surrounding connective tissue
205
Q

Characteristics of capillaries

A
  • 1-2 endothelial cells surrounding lumen
  • no muscular layer
  • pericytes
  • collagenous fibrils that connect capillary to adjacent connective tissue
206
Q

Two main types of capillaries

A
  1. Continuous

2. Fenestrated

207
Q

Transfer in continuous capillaries

A

pinocytotic vesicles

208
Q

Transfer in fenestrated capillaries

A

pores in the endothelial cells

209
Q

Vasoregulatory molecules that work on post-capillary venules

A

serotonin and histamine

210
Q

Vein characteristics

A
  • thin walled
  • often collapsed
  • intimal layer of endothelial cells
  • no inner elastic lamina
  • media: 2-4 layers of smooth muscle
  • adventitia: collagenous and blends with CT
211
Q

Characteristics of lymphatics

A
  • single, very thin endothelial layer
  • little discernable outer layer
  • lymph itself stains a light color
212
Q

Cardiac muscles have ____ nucleus and are much ____ in diameter and ____ than skeletal muscle fibers.

A

a single
smaller
shorter

213
Q

Distinguishing feature of cardiac muscle

A

intercalated disk

214
Q

Functions of intercalated disc

A
  1. physically ties together adjacent cells so they don’t pull apart when contracting
  2. contains gap junctions for the transmission of electric current
215
Q

Smooth muscle cells have ___ nucleus and are ___ than cardiac cells

A

a single

thinner (2-5 micrometer in diameter)

216
Q

Shape of smooth muscle cells

A

spindle with nucleus near center

217
Q

thin filaments

A

actin

218
Q

thick filaments

A

myosin

219
Q

Two regulatory proteins in muscle contraction

A

tropomyosin and troponin

220
Q

Structure of F acting

A

double stranded and helical

221
Q

Troponin and tropomyosin bind to ___

A

actin filaments

222
Q

Tropomyosin in ___ shaped and binds ____ actin molecules. Troponin binds to _____.

A

rod
6-7
one end of tropomyosin

223
Q

Structure of Myosin

A

6 proteins- 3 pairs

  • 1 pair of large, heavy chains
  • 2 pairs of small, light chains
224
Q

Heavy chains of myosin

A

long alpha-helical region with a globular head

225
Q

Short light chains of myosin are associated with

A

globular heads of heavy chains

226
Q

Thick filaments are ___ long and contain ____ myosins

A

1.6 um long

300-400

227
Q

Thin filaments are ___ long

A

1 um

228
Q

Relaxed state

A

binding of myosin to actin is prevented because binding site of actin is covered by tropomyosin

229
Q

Ca2+ rises->

A
  • troponin binds Ca2+ and undergoes conformational change

- Induces conformational change of tropomyosin to expose binding sites

230
Q

Myosin head binds actin… Does it need ATP to generate force?

A

NO

energy is released upon binding

231
Q

Shortening of sarcomere in one power stroke

A

8nm

232
Q

Binding of ATP allows myosin to ____

A

dissociate from actin and hydrolysis of ATP occurs putting myosin into a high energy state

233
Q

If each myosin-actin cycle results in a displacement of 8 nm, how do we get muscle shortening of centimeters?

A

(1) Lots of sarcomeres in series will summate linearly.

(2) Many myosin-actin cycles occur during a single contraction.

234
Q

The myosin in fast twitch muscle cycles about ___ times per second, but in slow muscle it only goes about ____ times per second.

A

20

5

235
Q

Increase of Ca2+ in smooth muscle

A

-Ca binds to calmodulin
Ca/Calmodulin binds Cam Kinase
-CaM kinase phosphorylates light chain of myosin

236
Q

Removal of Ca in smooth muscle

A

Ca pumps and Na-Ca exchangers in the sarcolemma.

237
Q

Dystrophin associaes with

A

actin and surface membrane

238
Q

Titin

A

links myosin to Z line

239
Q

Nebulin

A

associated with actin thin filaments and keeps them organized

240
Q

At the Z line ____ is a molecule that crosslinks actin filaments

A

alpha actinin

241
Q

Familial hypertrophic cardiomyopathy (FHC)

A

mutation in head region of myosin heavy chain OR troponin

242
Q

Synaptic contact of a cell near

A

center of cell

243
Q

action potential causes release of

A

ACh

244
Q

ACh binds to ___ and causes ___

A

ACh receptor

depolarization and opening of Na channels

245
Q

3 important molecules for signaling and energy in muscle contraction

A

ca
o2
ATP

246
Q

Mobile carrier of Ca

A

parvalbumin

247
Q

carrier of o2

A

Myoglobin

248
Q

____ and ____ with replenish ATP in high demands

A

creatine and phosphocreatine

249
Q

Two unusual structures have evolved for speed and storage

A

: transverse tubule system (t-system) and sarcoplasmic reticulum (SR; specialized smooth endoplasmic reticulum).

250
Q

Transverse tubule system

A
  • membrane structure that allows the action potential to propagate throughout the cross section of the cell.
251
Q

SR

A

where calcium is stored

252
Q

E-C coupling

A

membrane depolarization in the t-system is translated into Ca+2 release from the SR

253
Q

Contact of the SR with t-tubule called ____ and contains a protein called ____

A

terminal cisterna

calsquestrin (binds 50 Ca)

254
Q

At the apposition of the SR and the ttubule, there are proteins that are electron-dense and look dark in electron microscope pictures, and this region is called

A

the triad

255
Q

Receptor on t-tubule

A

dihydropyridine receptor (DHPR)

256
Q

Subunits of DHPR

A
  • voltage gated Ca channel
257
Q

Receptor on SR

A

RyR- ca release channel

258
Q

abnormal calcium release channel in the SR causes a disease called

A 
malignant hyperthermia (MH) (or also Central core disease)
-rise in body temp when given volatile anesthetics (halothane)
259
Q

Treatment of MH

A

intravenous dantrolene- blocks muscle contraction by blocking Ca+2 release from the SR

260
Q

Mechanism of MH

A
  • aesthetic triggers alteration of SR Ca release where it is independent of DHPR conformational change
  • steady Ca+2 leak from the SR activates the Ca+2 ATPase to pump Ca+2 back into the SR and a futile, heat-producing cycle occurs and is lethal if not corrected
261
Q

Mutation of DHPR

A

muscular dysgenesis

-look normal but cannot breathe

262
Q

Inject DHPR mice with DNA coding for DHPR

A

cells will contract when depolarized

263
Q

Muscle relaxation

A

Ca+2 ATPase pumps in the SR membrane transport Ca+2 back into the SR and bring cytoplasmic Ca+2 back to a low level (

264
Q

Why doesn’t smooth muscle need t-system or SR?

A

Smooth muscle cells are so thin that Ca+2 entering via Ca+2 channels in the surface membrane can easily diffuse to the center of the cell (however, some smooth muscle cells do have a rudimentary SR)

265
Q

Tension increases linearly as the amount of overlap between actin and myosin ____

A

increases

266
Q

When the shortening causes the actin filaments to interdigitate in the middle of the sarcomere

A

tension begins to decrease

267
Q

Muscles that perform fine movements (e.g. finger muscles or extraocular eye muscles) tend to have

A

small motor units

268
Q

Size recruitment of motor units during voluntary movement

A

small motor units are recruited first and progressively larger motor units are recruited as the strength of contraction is increased. This allows a fine control of movement.

269
Q

Cardiac and smooth muscle are linked by ____

A

gap junctions

270
Q

Three classes of skeletal muscle

A

slow, fast, and intermediate

271
Q

Slow fibers color

A

reddish- high myoglobin content

272
Q

Intermediate fibers are

A

fast with both glycolytic and oxidative enzymes

273
Q

Fast twitch fibers have

A

high glycolytic content

274
Q

3 ways to grade tension in skeletal muscle

A

(1) Increase the frequency of action potentials. This will increase tension until a maximal (tetanic) contraction is achieved. (2) Recruit additional motor units. This increases tension until all motor neurons innervating the muscle are stimulated.
(3) Changing the length of the muscle is a minor factor for skeletal muscle because it normally operates near the optimal length.

275
Q

Grading tension in cardiac and smooth muscle

A

both respond to neurotransmitters and hormone-like molecules. They are also strongly influenced by the length of the cell since this length is not fixed by attachments to bone

276
Q

Stem cells in skeletal muscle

A

Satellite cells

277
Q

Factor that stimulates proliferation of satellite cells

A

LIF

278
Q

connective tissue fibroblasts interact with satellite cells to

A
  • regulate proliferation

- prevent premature differentiation

279
Q

Repair of cardiac muscle

A

no satellite cells-> little to no repair

280
Q

Repair of smooth muscle cells

A

cells can dedifferentiate, enter mitosis and regenerate new muscle cells.

281
Q

Conversion of fast and slow twitch fibers

A

, the most that is observed is a shift from fast to the fast intermediate and an increase in the oxidative capacity of the cells

282
Q

Steps affected in muscle fatigue

A

(1) propagation of the action potential into the t tubule,
(2) release of Ca+2 from the SR,
(3) effect of Ca+2 on the myofilament interaction and
(4) force generation by the myofilaments

283
Q

Innervation of smooth muscle

A

Sympathetic and parasympathetic

284
Q

Transmitter responsible for relaxation of smooth muscle

A

NO

285
Q

NO is produced by

A

endothelial cells and some neurons

286
Q

NO binds to a receptor and increases levels of

A

cGMP

287
Q

Smooth muscle action potentials

A

Ca+2, not Na action potentials

288
Q

Multinucleated

A

Skeletal

289
Q

Length of cell (SK, C, SM)

A

SK: 2-3 cm
C: 50-100 um
SM: hundreds of um

290
Q

Diameter (SK, C, SM)

A

SK: up to 100um
C: 5-15 um
SM: 2-5 um

291
Q

Neurotransmitter:
SK:
C:
SM:

A

SK: ACh
C: ACh and norepinephrine
SM: ACh, NO, peptides

292
Q

big to small:

muscle fibers->

A

myofibril

293
Q

endomysium

A

separates muscle fibers

294
Q

perimysium

A

contains bundles of muscle fibers

295
Q

Epimysium

A

Around each muacle

296
Q

Myostatin

A

Inhibits muscle growth

297
Q

Myostatin is raised in ____ patients

A

AIDS

298
Q

volatile anesthetics MH

A

halothane

succinylcholine

299
Q

MH clinical manifestations

A
  • muscle rigidity
  • masseter spasm
  • increased co2
  • rhabodomyolysis
  • hyperthemia
300
Q

Dantrolene

A

treatment of MH

301
Q

Gower maneuver

A

used to diagnos DMD

302
Q

Creatinine kinase DMD

A

High

303
Q

Cardiopulmonary problem in DMD

A

Cardiomyopathy

304
Q

Treatment of muscular dystrophy

A
  • suppressing premature stop codons

- RNA target based therapies

305
Q

Majority of hypertrophic cardiomyopathy mutations are

A

Missense

306
Q

Muscle cell phenotype of someone with HCM

A
  • cardiomyocyte and cardiac hypertrophy
  • myocyte disarray-> function compromised
  • interstitial and replacement fibrosis-> propensity to arrhythmia
  • dysplastic intramyocardial arterioles-> ischemia
307
Q

Phenotype of HCM

A

-asymptomatic

308
Q

Clinical presentation of HCM

A
  • cardiac murmur
  • heart failure
  • Arrhythmia
309
Q

Functions of macrophages (4)

A

(i) engulf (phagocytose) invading microorganisms,
(ii) promote blood vessel formation (angiogenesis),
(iii) remodel damaged tissue,
(iv) remodel normal developing tissue and organs as part of their morphogenesis.

310
Q

Main function of fibroblasts

A

produce and secrete components of ECM

311
Q

Contents of matrix vesicles

A

ca
po4
alkaline phosphatases

312
Q

Length of sarcomere in resting muscle

A

2.4 um

313
Q

Most DMD mutations are

A

Large deletions

314
Q

Dystrophin

A
  • intracellular protein
  • Sk, SM, and C
  • Sarcolemma associated complex

M2M Unit 4 (2 decks)

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