PDFs Flashcards
(314 cards)
1
Q
The outer membrane of mitochondria is _____
A
semi-permeable
2
Q
Mitochondrial membranes are transported via ____ and ____ complexes
A
TOM and TIM
3
Q
GTPases involved in fusion
A
Mfn OPA1
4
Q
GTPases involved in fission
A
Fis1 and DRP
5
Q
Free energy released in oxidation of glucose
A
NADH
6
Q
Electrons transferred from NADH to ___ to form ____
A
O2 to form H2O
7
Q
Two parts of ATP synthase
A
f1 and F0
8
Q
F0 spans the ______ mitochondria membrane and forms a ______
A
inner
proton channel
9
Q
F1 is bound to ___ and ____
A
F0
is an actual enzyme that makes ATP
10
Q
Once made, ATP is transported out of mitochondria via___
A
ATP-ADP antiporter
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
12
Q
Damaged mitochondria make excessive amounts of ___
A
ROS
13
Q
Mitochondria quality is strictly controlled at three levels:
A
- mitochondrial proteases (MAAA, iAAA, and Lon) degrade misfolded proteins
- fusion with healthy mitochondria can fix it
- apoptosis
14
Q
Arsenic
A
inhibits oxidative phosphorylation and ATP production
15
Q
Mfn and OPA mutations
A
- autosomal dominant optic atrophy
- charcot- marie tooth type 2A
16
Q
Mutation in MAAA
A
Hereditary spastic paraplegia
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
18
Q
Categorization of CFTR mutations
A
5 main classes
19
Q
Most common mutation in CF
A
F508del
20
Q
Major cause of morbidity and mortality in CF
A
lung involvement
21
Q
depleted _______ layer in the lung leads to impaired ___________ and altered host defense
A
pericilliary
mucocilliary clearance
22
Q
CF- Sinus
A
chronic sinus infections, nasal polyps
23
Q
CF- lung
A
respiratory inections, bronchiectasis
24
Q
CF- pancreas-
A
exocrine pancreatic insufficiency
25
CF- GI
Distal ileal obstructive syndrome
26
Sweat chloride >___ mmol/L indicative of CF
60
27
Diagnosing CF
```
IRT/IRT/DNA
immunoreactive trysinogen (pancreatic enzyme)
```
28
Nutrition treatment CF
HIgh- calorie, protein, fat
| Supplementation of vitamins A, D, E, and K (fat soluble)
29
Lung treatment CF
airway clearance therapy
antibiotic therapy targetinf common CF related bacteria
Anti-inflammatory treatments
30
CFTR modulators
Target specific CFTR mutations
31
Mutation treated with Ivacaftor
G551D
32
Orkambi mutation
F508del
33
Median life expectancy CF
40
34
Basal bodies are ____
Microtubule rich cylinder shaped structures
35
Basal bodies are made of
9 triplet microtubules (A-B-C tubules)
36
Distal end of basal bodies responsible for
nucleating the cilium
37
Structural skeleton of cilium
Axoneme
38
Structure of axoneme
A-B tubules that form from a ans b tubules of basal body
39
function of axoneme
scaffolding
| tracks for movement within cilia
40
Linker of basal body to axonome and ciliary body
transition zone
41
"Gatekeeping" function of transition zone
limits diffusion of membrane and soluble proteins into and out of cilium
42
Part of cilia continuous with the cellular plasma membrane
ciliary membrane
43
mechanism of transport of signaling components within cilia
intragflagellar transport
44
proteins involved in movement to ciliary tip
Kinesin-2
| IFT-B
45
Ciliary retrograde transport proteins
dynein 2
| IFT-A
46
Two phases of ciliogenesis
1. centrioles/basal bodies assembled
| 2. Formation of cilium
47
Basal bodies are derived from
centrioles
48
Centriole that functions as basal body
Mother centriole
49
Ciliogenesis occurs during _____ of the cell cycle
G1 (or G0)
50
Ciliogenesis begins when the distal end of a basal body is capped by a _____
ciliary vesicle
51
What happens after a basal body is capped by a ciliary vesicle?
Microtubule doublets then assemble into the ciliary vesicle before the entire structure fuses with the plasma membrane of the cell
52
Motile cilia are required for the movement of fluid in the ____, _____, and _____ tracts
respiratory, neural, and reproductive
53
Motility of motile cilia is produced by ____
axonemal dynein dependent sliding motion between the doublet microtubules of the ciliary axoneme
54
Motile cilia microtubule arrangement
9+2
| Not all have this arrangement (Nodal)
55
The distinguishing factor between motile and immotile cilia is the presence of
axonemal dynein arms between the doublet microtubules
56
Non-motile, sensory or primary cilia microtubule arrangement
9 + 0
57
Pathway well established to signal through cilia
Hedgehog (Hh)
58
Hh target
Gli transcriptional activator
59
Downstream targets of Hh signaling
limb formation
bone formation and homeostasis
neurogenesis
60
Characteristics of ciliopathies (6)
1. rare
2. pleiotropic
3. Overlapping
4. structural
5. diverse
6. genetically complex
61
Two examples of ciliopathies
1. Bardet- biedi syndrome (BBS)
| 2. Polycystic kidney disease (PKD)
62
BBS is autosomal ____
recessive
63
BBS proteins participate in a protein complex that is required for
vesicle transport within the cilium
64
Symptoms of BBS
```
Photoreceptor degeneration
• Anosmia
• Mental retardation / Developmental delay
• Neural tube defects
• Obesity
• Hypogonadism
• Kidney defects
• Polydactyly
• Diabetes
```
65
PKD is autosomal ____
dominant (ADPKD) and recessive (ARPKD)
66
ARKPD is caused by _____ mutations
fibrocystin
67
ADKPD is caused by mutations in ____ and _____
polycistin 1 and polycistin 2
68
PKD genes encode
channel proteins responsible for calcium signaling
69
Symptoms of PKD
Renal cysts
• Liver and pancreas cysts
• Intracranial aneurysms
70
Epithelial tissues are a-
avascular
71
Functions of epithelia (7)
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
72
Tissue that faces blood/lymph
endothelium
73
sheets of cells that line the enclosed internal spaces of the body cavities are called
mesothelium
74
____ layer of all mucosa is epithelium
Surface
75
Examples of organized comprised of epithelial cells that are the primary functional units
liver, pancreas, kidney
76
Epithelia are derived from which germ layers>
All three
77
Two layers of mucosae
1. outer epithelium
| 2. CT underneath- lamina propia
78
Lamina propia contain a lot of ____
immune system cells and small blood vessels
79
Below lamina propia
submucosa
80
Simple epithelia
have all cells arranged in a single layer or sheet
81
Stratified epithelia
have more than one layer of cells in which cells of the outer layers do not directly contact the basal lamina.
82
-Pseudostratified epithelia
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
83
-Squamous cells
e flattened cells
84
-Transitional epithelia
(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
85
Key core proteins of tight junctions
occludins and claudins
86
Adherence junctions contain specific ___ that link to ___ filaments
Cadherins
| actin filaments and other signaling proteins
87
Desmosomes
Promote mechanical strength and resist shearing forces and promote the structural organization of the epithelial sheet
88
Core components of desmosomes
Cadherins that link to intermediate filaments
89
Key aspects of epithelial polarity
1. plasma membrane composition is locally separated into domains
2. Cytoplasm is polarized
90
endocytosis of substances from one membrane region, followed by trans-cellular transport of the vesicles and their exocytosis from another membrane region
transcytosis
91
Apical surface modifications
1. microvilli
| 2. cilia
92
Unusual type of microvillus found in epididymis and sensory cells in ear
stereocilia- not related to cilia
93
microvilli contain ___, while cilia contain ____
actin
| microtubules
94
Basal laminae are formed by a special type of network- forming ____
collagen
95
Glycoproteins common to basal laminae
laminins and enactin
96
Important functions of basal laminae
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.
97
Epithelial cells directly connect to basal laminae by attachment of
hemidesmosomes and focal adhesions on the basal surface of epithelial cell to components of the basal lamina
98
for connections between basal surface and basal lamina
integrins
99
Different integrins of focal adhesions connect to ____ inside the epithelial cell
Actin filaments
100
Most, if not all epithelia contain stem cells that
(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.
101
Stem cell daughters that proliferate themselves
transit amplifying cells
102
A specific stem cell type, its intermediate progeny, and their differentiated progeny are collectively called
cell lineage
103
Tarceva (erlotinib)
inactivates the EGF receptor and is commonly used to treat lung and pancreatic cancers).
104
Two major types of epithelial glands
1. exocrine
| 2. endocrine
105
Exocrine secrete on the ___ side
apical
106
Two ways glands secrete
1. exocytosis (merocrine or apocrine glands)
| 2. Total cell disintegration (holocrine glands, secrete entire contents)
107
Exocrine glands are typically ____
multicellular
108
Two main components of exocrine glands
1. Secretory units
| 2. Ducts
109
Secretory units can be organized into bowl or flask-shaped lobules called.. Or tubes
Alveoli or acini
| tubular
110
Ducts
tubular structures that emanate from the secretory units
111
Glands that possess a single duct are classified as ______ glands, whereas those with multiple branched ducts are called ______ glands.
Simple
| Compund
112
3 general exocrine glands of body tubes
1. Mucous
2. Serous
3. Mixed
113
During endocrine secretion, hormones must cross ____ and _____ of the wpithelium to reach the blood stream
basal surface
| basal lamina
114
Pemphigus
autoimmune disease in which antibodies are produced against components of desmosomes in skin, leading to extensive blistering
115
Cancers of epithelial origin
carcinomas
116
Cancers derived from glandular epithelium
adenocarcinoma
117
Connective tissue near body surface
Superficial fascia
118
Function of connective tissue
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)
119
Two classes of cells in connective tissue
1. Resident cells of the CT family
| 2. Immigrant blood-derived cells
120
6 examples of immigrant blood-derived cells
1. lymphocytes- acquired immunity
2. macrophages- phagocytosis
3. neutrophils and eosinophils- bacterial defense
4. mast cells- promote swelling
5. Osteoclasts- bone resorption
121
Components of ECM
(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.
122
Most abundant structural fibers of ECM
Collagen
123
Collagen fibers are formed from ___ intertwined polypeptides, individually called ___
3
| alpha chain
124
3 types of collagen fibers
1. Fabrillar
2. Fibril associated
3. Network-forming
125
Loose connective tissues contain
thin collagen fibrils that are relatively sparse, and are arranged in irregular lattices.
126
Dense connective tissues contain ______ that are very abundant relative to ground substance, and have a ___ number of cells.
thick collagen fibrils
| low
127
The individual polypeptides of collagen are assembled into a triple helix where?
Intracellularly
128
Extracellular modifications of collagen
N and c terminals cleaved by proteases
formation of bundles
enzymes catalyze chemical cross links (increase tensile strength)
129
Elastic fibers contain proteins ___ and ___
elastin and fibrillin
130
Major components of ground substance
1. Proteoglycans
2. other secreted proteins and glycoproteins
3. Inrganic and small organic solutes
4. Water
131
3 properties of GAGs
1. Negatively charged
2. Rigid structure allows them to form gels
3. some can bind to ans activate/inactivate other proteins
132
Events in wound healing
1. Inflammation and blood clotting
2. New tissue formation
3. Tissue remodeling
133
Signaling compounds in inflammation
(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
Histamine is secreted by
mast cells
135
histamines promote
endothelial permeabilization
136
Matrix of bone is ___ or ___
mineralized or calcified
137
Bone is ____, while cartilage is much _____
dynamic
| less dynamic
138
Cartilage is ___ in its matrix
avascular
139
two main functions of cartilage
1) to provide a resilient but pliable support structure. (2) to direct the formation and growth of bone
140
Cartilage cells that make matrix and tissue
Chondroctes
141
CT that surrounds cartilage
pericondrium
142
Isolated compartment in which chondrocytes reside
lacuna
143
Cartilage are distinguished based on differences in their ____
Matrix
144
3 types of cartilage
1. Hyaline cartilage
2. Elastic cartilage
3. Fibrocartilage
145
Hyaline cartilage contains collagen that forms relatively____ fibrils that are generally arranged in an _______
thin
| irregular three dimensional pattern
146
Ground substance of hyaline cartilage is rich in ____ and ____
```
proteoglycans
hyaluronic acid (promotes hydration and flexibility)
```
147
Structural properties of Hyaline ECM
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
Distinguishing feature of elastic cartilage from hyaline cartilage
elastic fibers and sheets of elastic material
149
Fibrocartilage
large bundles of regularly arranged collagen
150
Bone marrow consists of either __ or ___
```
hematopoietic tissue (red bone marrow)
adipose cells (white bone marrow)
```
151
The inner surface where trabeculae contact internal soft tissue is called the
endosteum
152
Specialized cell types of bone cells
1. osteoprogenitor
2. osteoblasts
3. osteocytes
4. osteoclasts
153
Osteoprogenitor cells
stem cells
154
osteoblasts
line the inner layers of both periosteal and endosteal surfaces where bone growth or remodeling is occurri
155
osteoblasts secrete un-mineralized ECM called ___
osteoid
156
Osteoblast vesivles containing enzymes that initiate bone calcification
matrix vesicles
157
Osteoblasts are connected by
gap junctions
158
cells derived from oseoblasts
Osteocytes
159
Unlike chondrocytes, osteocytes do not __
divide
| arrest in G0
160
Osteocytes extend long processes through tiny channels called ___
canaliculi
161
Osteoclasts are derived from
monocytes in the blood
162
Functions of osteoclasts
(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
ECm of bone is uniques since it contains large amounts of crystallized ___ and ____
Ca2+
| PO4 (hydroxyapatite)
164
In long bones, channels that traverse the long axis through compact bone are called
Haversian canals
165
Lammelae + haversion canal
osteon
166
canals that link together haversian canals and the periosteum
Volkmann's canals
167
Two ways that bone is formed
1. Intramembranous ossification
| 2. Endochondral ossification
168
Intramembranous ossification
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
Endochondral ossification
cartilage model
170
Formation of the cartilage model
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
Two different growth methods cartilage
1. Appositional growth- growth at the surface
| 2. Intersitial growth- growth from within
172
Groups of chondroctyes within a lacuna or still close together are actually clones of cells derived from mitosis and are called
isogenious groups
173
Crucial region of continued growth in the length of the bone
epiphyseal plate
174
Bone growth stops when proliferation of the ____ stops
cartilage
175
Once growth stops, only a sheath of non-proliferative cartilage remains at the very end (the articular surface) of the epiphysis; this is called
Articular cartilage
176
Growth in the diameter of bone occurs in the ___
periosteum
| appositional growth
177
In adult bone, most of the resorptive activity occurs at the ____ surface
endosteal
178
Osteoblasts initiate mineralization of the osteoid by
secreting matrix vesicles
179
Bone and cartilage regulation is mediated by:
1. short range singals (BMPs)
2. Long range signals from endocrine glands
3. Mechanical stress
4. Neuronal stimulation
180
BMPs
trigger intracellular protein phosphorylation that alters gene expression, which in turn promotes specific patterns of differentiation
181
Parathyroid hormone stimulates
calcium liberation
182
calcitonin
stimulates calcium uptake
183
Vitamin D important for
Systems that promote calcium uptake from the intestine
184
Lung cancer screening
Low dose CT
185
Lung cancer screening caused a __ reduction in cancer mortality and ___ reduction in all cause mortality
20%
| 7%
186
Problem with lung cancer screening
False positive rates- 95%
187
Subtypes of lung cancer
Squamous carcinoma- 30%
Adenocarcinoma- 40%
Small Cell- 15%
Large cell + other- 15%
188
2 types of EGFR inhibitors
antibody- extracellular
| Tyrosine kinase inhibitors- intracellular
189
ALK mutation in lung cancer
ALK gene on chromosome 2 fuses with EML 4
detected with FISH
190
_____ is a receptor on a T cell that can interact with the _____ receptor on a cancer cell. This interaction ____ t cell function
PD-1
PD-L1
inhibits
191
2 PD-L1 antibodies
Nivolumab
| Pembrolizumab
192
Two types of resistance mechanisms
Primary- already in tumr
| Acquired- developed during therapy
193
aorta to capillaries:
_____ # of vessels
______ overall cross sectional diameter
2-3 billion fold increase in
| 500 fold increase in cross sectional diameter
194
Blood flow is slowest in _____
capillaries and venules
195
tunica intima made of:
endothelial cells
| layer of elastic and loose collagenous tissues containing intimal cells (in larger vessels)
196
Tunica media made of:
multiple layers of elastic laminae, smooth muscle cells, or collagen
197
Tunica adventitia made of:
```
Collagenous tissue
Vasa vasorum (in larger vessels)
```
198
Smooth muscle is found in the media from the aorta to the ____
Arterioles
199
The elastic layers are crucial to permit ____
l to permit expansion of the vessels after systolic contraction of the heart, dampening the systolic blood pressure
200
Smooth muscle, particularly in the arterioles, permits
control of blood flow to capillary beds
201
How many elastic layers are in the aorta
Typically around 30-40
202
How may elastic layers in muscular arteries?
two well-defined
203
Characteristics of smaller muscular arteries
- lose outer elastic lamina
- relatively large layer of smooth muscle
- adventitia same width as media and merges with surrounding connective tissue
204
Arteriole characteristics
- 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
Characteristics of capillaries
- 1-2 endothelial cells surrounding lumen
- no muscular layer
- pericytes
- collagenous fibrils that connect capillary to adjacent connective tissue
206
Two main types of capillaries
1. Continuous
| 2. Fenestrated
207
Transfer in continuous capillaries
pinocytotic vesicles
208
Transfer in fenestrated capillaries
pores in the endothelial cells
209
Vasoregulatory molecules that work on post-capillary venules
serotonin and histamine
210
Vein characteristics
- 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
Characteristics of lymphatics
- single, very thin endothelial layer
- little discernable outer layer
- lymph itself stains a light color
212
Cardiac muscles have ____ nucleus and are much ____ in diameter and ____ than skeletal muscle fibers.
a single
smaller
shorter
213
Distinguishing feature of cardiac muscle
intercalated disk
214
Functions of intercalated disc
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
Smooth muscle cells have ___ nucleus and are ___ than cardiac cells
a single
| thinner (2-5 micrometer in diameter)
216
Shape of smooth muscle cells
spindle with nucleus near center
217
thin filaments
actin
218
thick filaments
myosin
219
Two regulatory proteins in muscle contraction
tropomyosin and troponin
220
Structure of F acting
double stranded and helical
221
Troponin and tropomyosin bind to ___
actin filaments
222
Tropomyosin in ___ shaped and binds ____ actin molecules. Troponin binds to _____.
rod
6-7
one end of tropomyosin
223
Structure of Myosin
6 proteins- 3 pairs
- 1 pair of large, heavy chains
- 2 pairs of small, light chains
224
Heavy chains of myosin
long alpha-helical region with a globular head
225
Short light chains of myosin are associated with
globular heads of heavy chains
226
Thick filaments are ___ long and contain ____ myosins
1.6 um long
| 300-400
227
Thin filaments are ___ long
1 um
228
Relaxed state
binding of myosin to actin is prevented because binding site of actin is covered by tropomyosin
229
Ca2+ rises->
- troponin binds Ca2+ and undergoes conformational change
| - Induces conformational change of tropomyosin to expose binding sites
230
Myosin head binds actin... Does it need ATP to generate force?
NO
| energy is released upon binding
231
Shortening of sarcomere in one power stroke
8nm
232
Binding of ATP allows myosin to ____
dissociate from actin and hydrolysis of ATP occurs putting myosin into a high energy state
233
If each myosin-actin cycle results in a displacement of 8 nm, how do we get muscle shortening of centimeters?
(1) Lots of sarcomeres in series will summate linearly.
| (2) Many myosin-actin cycles occur during a single contraction.
234
The myosin in fast twitch muscle cycles about ___ times per second, but in slow muscle it only goes about ____ times per second.
20
| 5
235
Increase of Ca2+ in smooth muscle
-Ca binds to calmodulin
Ca/Calmodulin binds Cam Kinase
-CaM kinase phosphorylates light chain of myosin
236
Removal of Ca in smooth muscle
Ca pumps and Na-Ca exchangers in the sarcolemma.
237
Dystrophin associaes with
actin and surface membrane
238
Titin
links myosin to Z line
239
Nebulin
associated with actin thin filaments and keeps them organized
240
At the Z line ____ is a molecule that crosslinks actin filaments
alpha actinin
241
Familial hypertrophic cardiomyopathy (FHC)
mutation in head region of myosin heavy chain OR troponin
242
Synaptic contact of a cell near
center of cell
243
action potential causes release of
ACh
244
ACh binds to ___ and causes ___
ACh receptor
| depolarization and opening of Na channels
245
3 important molecules for signaling and energy in muscle contraction
ca
o2
ATP
246
Mobile carrier of Ca
parvalbumin
247
carrier of o2
Myoglobin
248
____ and ____ with replenish ATP in high demands
creatine and phosphocreatine
249
Two unusual structures have evolved for speed and storage
: transverse tubule system (t-system) and sarcoplasmic reticulum (SR; specialized smooth endoplasmic reticulum).
250
Transverse tubule system
- membrane structure that allows the action potential to propagate throughout the cross section of the cell.
251
SR
where calcium is stored
252
E-C coupling
membrane depolarization in the t-system is translated into Ca+2 release from the SR
253
Contact of the SR with t-tubule called ____ and contains a protein called ____
terminal cisterna
| calsquestrin (binds 50 Ca)
254
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
the triad
255
Receptor on t-tubule
dihydropyridine receptor (DHPR)
256
Subunits of DHPR
- voltage gated Ca channel
257
Receptor on SR
RyR- ca release channel
258
abnormal calcium release channel in the SR causes a disease called
```
malignant hyperthermia (MH) (or also Central core disease)
-rise in body temp when given volatile anesthetics (halothane)
```
259
Treatment of MH
intravenous dantrolene- blocks muscle contraction by blocking Ca+2 release from the SR
260
Mechanism of MH
- 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
Mutation of DHPR
muscular dysgenesis
| -look normal but cannot breathe
262
Inject DHPR mice with DNA coding for DHPR
cells will contract when depolarized
263
Muscle relaxation
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
Why doesn't smooth muscle need t-system or SR?
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
Tension increases linearly as the amount of overlap between actin and myosin ____
increases
266
When the shortening causes the actin filaments to interdigitate in the middle of the sarcomere
tension begins to decrease
267
Muscles that perform fine movements (e.g. finger muscles or extraocular eye muscles) tend to have
small motor units
268
Size recruitment of motor units during voluntary movement
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
Cardiac and smooth muscle are linked by ____
gap junctions
270
Three classes of skeletal muscle
slow, fast, and intermediate
271
Slow fibers color
reddish- high myoglobin content
272
Intermediate fibers are
fast with both glycolytic and oxidative enzymes
273
Fast twitch fibers have
high glycolytic content
274
3 ways to grade tension in skeletal muscle
(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
Grading tension in cardiac and smooth muscle
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
Stem cells in skeletal muscle
Satellite cells
277
Factor that stimulates proliferation of satellite cells
LIF
278
connective tissue fibroblasts interact with satellite cells to
- regulate proliferation
| - prevent premature differentiation
279
Repair of cardiac muscle
no satellite cells-> little to no repair
280
Repair of smooth muscle cells
cells can dedifferentiate, enter mitosis and regenerate new muscle cells.
281
Conversion of fast and slow twitch fibers
, 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
Steps affected in muscle fatigue
(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
Innervation of smooth muscle
Sympathetic and parasympathetic
284
Transmitter responsible for relaxation of smooth muscle
NO
285
NO is produced by
endothelial cells and some neurons
286
NO binds to a receptor and increases levels of
cGMP
287
Smooth muscle action potentials
Ca+2, not Na action potentials
288
Multinucleated
Skeletal
289
Length of cell (SK, C, SM)
SK: 2-3 cm
C: 50-100 um
SM: hundreds of um
290
Diameter (SK, C, SM)
SK: up to 100um
C: 5-15 um
SM: 2-5 um
291
Neurotransmitter:
SK:
C:
SM:
SK: ACh
C: ACh and norepinephrine
SM: ACh, NO, peptides
292
big to small:
| muscle fibers->
myofibril
293
endomysium
separates muscle fibers
294
perimysium
contains bundles of muscle fibers
295
Epimysium
Around each muacle
296
Myostatin
Inhibits muscle growth
297
Myostatin is raised in ____ patients
AIDS
298
volatile anesthetics MH
halothane
| succinylcholine
299
MH clinical manifestations
- muscle rigidity
- masseter spasm
- increased co2
- rhabodomyolysis
- hyperthemia
300
Dantrolene
treatment of MH
301
Gower maneuver
used to diagnos DMD
302
Creatinine kinase DMD
High
303
Cardiopulmonary problem in DMD
Cardiomyopathy
304
Treatment of muscular dystrophy
- suppressing premature stop codons
| - RNA target based therapies
305
Majority of hypertrophic cardiomyopathy mutations are
Missense
306
Muscle cell phenotype of someone with HCM
- cardiomyocyte and cardiac hypertrophy
- myocyte disarray-> function compromised
- interstitial and replacement fibrosis-> propensity to arrhythmia
- dysplastic intramyocardial arterioles-> ischemia
307
Phenotype of HCM
-asymptomatic
308
Clinical presentation of HCM
- cardiac murmur
- heart failure
- Arrhythmia
309
Functions of macrophages (4)
(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
Main function of fibroblasts
produce and secrete components of ECM
311
Contents of matrix vesicles
ca
po4
alkaline phosphatases
312
Length of sarcomere in resting muscle
2.4 um
313
Most DMD mutations are
Large deletions
314
Dystrophin
- intracellular protein
- Sk, SM, and C
- Sarcolemma associated complex
