Unit 4 Flashcards
(239 cards)
1
Q
Mitochondrial membrane permeability
A
Outer membrane: super permeable
Inner membrane: not very permeable
2
Q
Infoldings in mitochondrial inner membrane
A
cristae
3
Q
TOM
A
Translocase of outer membrane
passive transport
4
Q
TIm
A
Translocase of inner membrane
ATP-dependent
Targeting sequence binds to TIM and opens the pore, only that protein will fit, and it’ll be fed through as a polypeptide strand.
5
Q
Mitochondrial Fusion cellular GTPases
A
OPA1 and Mfn
6
Q
Mitochondrial Fission cellular GTPases
A
Fis1 and Drp
7
Q
F0 ATP synthase subunit
A
protein complex that spans the inner mitochondria membrane and contains a proton channel
8
Q
F1 ATP synthase complex
A
bound to F0, enzyme that actually makes ATP from ADP and phosphate
9
Q
Number of proton transfers needed to make 1 ATP
A
3
10
Q
How is ATP transported out of the mitochondria?
A
ATP/ADP transporter
11
Q
Role of mitochondria in cell death (apoptosis)
A
cell damage induces Bak/Bax-permeabilization of the outer mitochondrial membrane, which leads to cytochrome c release, which assembles an apoptosome
12
Q
Role of mitochondria in necrosis
A
ischemic injury leads to MPTP-dependent permeabilization of the inner and outer mitochondrial membrane resulting in cytochrome release and elimination of the proton gradient, which prevents ATP synthesis and actually causes ATP synthase to reverse directions and use things up more quickly!
13
Q
Mitochondria and quality control
A
1) mitochondrial proteases degrade misfolded proteins (mAAA, iAAA, Lon)
2) mitochondria can be fixed by fusing with healthy mitochonria
3) mitochondria can be eliminated by mitophagy
14
Q
Why is mitochondrial QC important?
A
Mitochondrial damage and resulting increase in RUS is related to increased senescence and increased sensitivity to neuronal degeneration
15
Q
Mitochondrial associated disease
A
mutation in OPA1 causes dominant optic atrophy
mutation in Mfn2 gene causes Charcot-Marie-Tooth neuropathy
mAAA protease mutation –> hereditary spastic paraplegia
16
Q
Asenic mxn
A
inhibits oxidative phosporylation and ATP production
17
Q
3 functions of mitochondria
A
1) ATP generation
2) Apoptosis
3) regulation of intracellular Ca2+
18
Q
Outer membrane mitochondrial import
A
GIp= general import pore
Tom 70 and Tom 20 are import proteins
19
Q
mtHSP70
A
recognizes the sequence for inner mitochondrial membrane import, binds it and TIM, hydrolyzes ATP, and pulls the protein through the membrane
20
Q
ATP synthase structure
A
F1: 3 α and 3 β subunits, spins around and goes through 3 conformations
1) binds ADP
2) squishes phosphate and ADP together
3) ATP gets released
21
Q
Cytochrome C and apoptosis
A
if cytochrome C is OXIDATED, it’ll form an apoptosome. It’s reversible if it’s small enough by reduction
22
Q
Blood supply of epithelial cells
A
Epithelial cells are avascular. Nutrients and oxygen diffuse through basal lamina and connective tissue to reach epithelial cells
23
Q
Epithelial funtions (7)
A
1) Barrier
2) Selection absorption and transport
3) Selective secretion
4) Movement of particles and movement through passageways
5) Biochemical modification of molecules
6) Communication to/from other tissues and organs
7) reception of sensory stimuli
24
Q
endothelium
A
a tissue that faces blood and lymph
25
mesothelium
sheets of cells that line enclosed internal spaces of the body cavities
26
Organs that are composed mostly of epithelial cells in which epithelia are primary functional units
Liver, kidney, pancreas
27
Developmental origins of epihthelia
Developed from all 3 primary germ layers
There's a lot of fluctuation in where the epithelia goes through early development.
-Many cells undergo epithelial to mesenchymal transition
28
Exceptions to generalized epithelia/CT/muscle/nerve relationships
- Some specialized neurons make contact with specific epithelial cells (ie taste buds)
- dendritic cells can infiltrate epithelia and migrate in and out of CT and can enter blood or lymph
29
lamina propria
the CT directly under the epithelium; typically contain lots of immune cells and small blood cells
30
submucosa
Layer of CT deep to the lamina propria. Typically contains larger muscles/vessels/nerves
31
Simple epithelia
all cells arranged in a single layer or sheet.
32
Stratified epithelia
more than one layer of cells in which cells of the outer layers do not directly contact the basal lamina.
33
pseudostratified
a special case where some cells do not reach the free surface
(giving a stratified appearance), but all directly rest on the basal lamina
34
Cell shapes relative to apical/basal axis
squamous=flat
cuboidal=cube-like
columnar=taller than wide
35
Naming stratified epithelia
Name them according to outer layer
36
Transitional epithelia (in bladder)
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.
37
Tight junctions
Key core proteins are claudins and occludins
| In some epithelia the "tightness" of the barrier is regulated
38
Adherence junctions
Promote attachment, but also polarization, morphological organization and stem-cell behavior
cadherins link to actin filaments
and interact with other cells' cadherins and intracellular proteins
39
Desmosomes
Promote mechanical strength
| Contain a different type of cadherins that link to intermediate filaments and adapter proteins
40
location of tight junction complexes
Typically toward the apical side of cells
41
Are the basal and lateral membranes the same in protein composition, etc.
Not necessarily. Sometimes they're different
42
Transcytosis
Transfer of vesicles from one side of the epithelium to the other
43
Microvilli
Protrusions that contain actin bundles connected to internal cytoskeleton
-Primary function= increase surface area
44
Stereocilia
a special type of microvilli found in the epididymis and sensory cells in ear.
45
Primary cilium
1 non-motile, microtubule based extension found on many cell types
-promote/organize signal transduction systems that control cell division, fate, and fxn
46
motile cilia
micotubule extensions that move like a boat oar to move mucus and other materials along.
47
Sensory cilia
not motile, have sensory fxn. ie. hair cells in ear
48
Location of villi and cilia
typically apical membrane. Sometimes there will be pockets for surface area in the basolateral membrane as well
49
Basal lamina
Formed by a special type of network-forming collagen (Type IV) interwoven with glycoproteins, laminins, and entactin
50
Basal laminae functions
- Attachment
- selective filtration to/from epithelia
- necessary for establishment of cell polarity
- "highways" for cells migrating through CT
- barrier to movement of microbes and cancer cells to other tissues
- control gene expression to effect proliferation or development
- Control development of epithelial cells by providin g a"tissue scaffolding" function (essential for repair following disease/injury)
51
Attachments of epithelial cells to basal laminae
hemidesmosomes (integrin attaches to IF's) and focal adhesions (integrins attach to actin) on basal surface
**all of these are made primarily from integrins*
=Focal adhesions regulate polarity and function through signaling, and are probably important in healing/cell turnover
52
Three qualities of all epithelial stem cells
(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.
53
Transit amplifying cells
- Daughter cells from stem cells that also proliferate, often at a faster rate
- They themselves produce differentiated cells
54
Cell lineage
A specific stem cell type, its intermediate progeny, and their differentiated progeny
55
Epithelial stem cell signaling source
secreted by cells within the same epithelium or in nearby CT
56
Core groups of signaling pathways that control tissue development
Wnt, Sonic Hedgehog, TGFβ, Notch, FGF, receptor tyrosine kinase family
57
Tarceva (erlotinib)
a lung and pancreatic cancer treatment
| inactivates EGF receptor
58
2 mechanisms of glandular secretion
1) Exocytosis
| 2) Total cellular disintegration (these glands are called holocrine glands)
59
Exocrine glands
secrete on the apical side of epithelium, generally multicellular (but some are unicellular ie Goblet cells)
60
Exocrine secretory units
bowl/flask shaped: alveoli/acini->alveolar/acinar gland
| tubes: tubular gland
61
Ducts
Tubular structure that emanates from the secretory unit, pathway for secretion to reach its destination
1 duct--> simple gland
>1 duct--> compound gland
62
3 types of exocrine glands
1) mucous--> viscous glycoprotein produced
2) serous--> watery/ salty fluid is produced
3) mixed--> both types of secretions released
63
Endocrine glands
-No ducts, secrete directly into blood stream
64
Organization of endocrine gland
generally a clump of cell embedded with surrounding CT containing extensive capillary networks (each clump surrounded by a basal lamina)
65
Direction of endocrine secretions
Typically basolateral (hormone must cross basal lamina)
66
Regulation of exocrine/endocrine glands
Regulated by autonomic input, blood hormones, or both
| Endocrine secretions are tightly regulated, exocrine less so
67
carcinoma
cancer of epithelial origin
68
adenocarcinomas
cancers developed from glandular epithelium
69
Typical progression of tumors
Tumors most commonly develop within an epithelial sheet but then can metastasize
70
Treatment targets for carcinomas
1) development signaling systems (wnt, EGF, notch)
2) internal cell cycle control factors
3) factors that control DNA repair and apoptosis
71
Epithelia and wound healing
- If basal epithelial stem cells and lamina are intact--> intrinsic mxns work!
- If damaged extensively, skin grafts may be required.
72
Cilia Base anchor
Basal bodies/centrioles
- microtubule rich cylindrical structures formed from nine triplet microtubules
- Polarized structure: proximal end forms first, distal-end nucleates the cilium
73
Axoneme
- structural skeleton of the cilium
- 9 fold symmetry
- Each individual microtubule subunit contains A-B tubules
- Plus ends at ciliary tip
- provide tracks for movement within cilia
74
Linkage domain/Transition zone of cilia
"gatekeeper" of the cilia
- attaches basal body to axoneme and ciliary membrane
- Limits diffusion of both membrane and soluble proteins into cilia
* *many disease mutations occur in this domain**
75
Ciliary membrane
compositionally distinct from plasma membrane because of transition zone
76
Intraflagellar transport
Anterograde: Kinesin 2 and IFT-B
Retrograde: dynein 2 and IFT-A
Lipid rafts are transported back and forth
77
Which centrosome becomes the basal body?
The older/mother centrosome
78
When in the cell cycle are cilia formed? replicated?
Formed- Early G1/G0
| Replicated-S (along with DNA)
79
Steps of ciliogenesis
1) Mother centriole recruits vesicle from the golgi ("ciliary vesicle")
2) Doublet appendages form and elongate
3) The structure hits the plasma membrane and fuses, axoneme is formed.
80
Motile cilia structure
Typically have a 9+2 axonemal microtubule arrangement (but a few exceptions are 9+0)
81
Distinguishing factor between motile and sensory cilia
Motile cilia have axonemal dynein arms
| Primary/Sensory are 9+0 without axonemal dynein arms
82
3 types of stimuli detected by receptors in cilia
1) Physical stimuli (mechanical, temp, osmolarity)
2) Light
3) Chemical stimuli
83
Reasons why cilia is an optimal signaling molecule
- Concentration of signal
- localized/polarized signal
- fluid mechanics (able to detect signals further from surface)
- can detect mechanical flow
84
Hedgehog signaling pathway
- Well established to act through cilia
| - Target is the Glioma tumor transcriptional activator
85
Hedgehog downstream targets
Limb formation
bone formation
neurogenesis
86
Ciliary node
- an invagination of ciliary cells that forms during gastrulation
- cells beat in a rotary fashion producing a net leftward flow of signaling molecules
- Determines laterality of body
87
Bardet Biedl Syndrome
Autosomal recessive
-19+ genes id'd
-BBS proteins affect vesicle transport in the clilum
Symptoms: photoreceptor degeneration, anosmia, developmental delay, neural tube defects, obesity, hypogonadism, kidney defects, diabetes, situs inversus
88
Polycystic kidney disease
Autosomal dominant (polycystin 1 or 2 mutation) or recessive (fibrocystin mutation)
- genes encode Ca++ that sense mechanical flow of urine in kidney lumen
- renal, pancreatic, and hepatic cysts and intracranial aneurysms
89
CF genetics
Autosomal recessive
All mutations occur in CFTR gene (there are many)
ΔF508 is the most common mutation
90
CFTR function
Chloride ion channel
controls the movement of salt and water in/out of cells
Loss of this movement alters host defense in the lung
91
CF Class 1
No CFTR synthesis occurs
92
CF Class 2
Block in processing- CFTR synthesis starts but processing isn't completed/ membrane insertion does not occur
93
CF class 3
Block in gating
| Channel is made and put in the membrane, but Chloride can't actually get through at all
94
CF class 4
Altered conductance
| CFTR is made and inserted, but it doesn't conduct chloride as well
95
CF class 5
Reduced synthesis
96
Newborn screen in in colorado
IRT/IRT/DNA
| IRT= immunoreactive trypsinogen, a pancreatic enzyme
97
CF diagnosis
```
Diagnosed through:
- Positive NBS OR
- ≥1 clinical feature of CF OR
- Family hx of CF
PLUS
- Sweat Cl ≥ 60 mmol/L AND/OR
- 2 CF mutations
```
98
GI treatments for CF
- Salt supplement
| - Pancreatic enzyme supplement
99
Lung treatments for CF
Daily airway clearance (percussive therapy, inhaled pulmozyme, inhaled saline/bronchodilators)
Antibiotic therapy for common CF related bacteria
100
Anti-inflammaory treatments
Ibuprofen
| Chronic azithromycin
101
Ivacaftor
CFTR "potentiator" FDA approved for people 2 and over with Class III CF
G551D protein mutation
102
Orkambi (Lumacaftor/Ivacaftor)
Combination CFTR "corrector" and "potentiator" for Class II CF ( 2 copies of the F508del mutation)
103
Mesenchymal cells
stem cell precursors to all CT family cells
| Most active during embryogenesis, a few will persist to adulthood
104
Fibroblasts
pre-eminent cells of most connective tissues in body
105
ECM functions (6)
a. control of epithelial cell polarization and shape
b. guidance and regulation of cell migration through matrix
c. control of cell proliferation, differentiation, metabolism
d. defense against infectious agents
e. control of tissue formation, organization, modification
f. Control of inflammation and repair due to injury
106
Myofibroblasts
derivatives of fibroblasts capable of smooth-muscle like function (Often found in CT sites that require contractile function)
often generated at the sight of wounds, contributes to shrinkage of scar tissue
107
Fibroblast derivatives
Adipocytes
108
Adipocytes
store fat as energy for other cell types
"white fat'-adults
"brown fat"= a distinct type that converts fatty acids to heat in kids
109
Osteoblasts
Make bone
110
Osteocytes
Are left behind and actually hang out in bone
111
Chondrocytes
make cartilage
112
Smooth muscle cells
Exist in CT
| A few of them (esp ones in blood vessel walls) make ECM components
113
Cells that secrete ECM components
msenchymal cells, fibroblasts, myofibroblasts, adiiposytes, osteoblasts/cytes, chondrocytes, some smooth muscles
114
Lymphocytes
central to acquired immunity
115
Macrophatges
large" engulfing cells that phagocytose, signal for angiogenesis, remodel damaged tissue and normal tissue as part of development
116
neutrophils and eosinohpils
white blood cells important for defense against microorganisms
117
Mast Cells
Secretory cells that release various substances, including vasodilators that promote swelling in CT's (important in edema and allergies)
118
Osteoclasts
phagocytotic cells derived from blood monocytes, function in bone resorption
119
Immigrant Blood derived cells in CT
Lymphocytes, macrophages, eosinophils and neutrophils, mast cells, osteoclasts
120
Fibrillar collagen
assembled into large bundles (aligned head to tail for length, stacked for thickness.)
Great tensile strength, most abundant in body, Type 1 collagen
121
3 types of collagen
Fibrillar, fibril-associated, and network-forming
122
Fibril associated collagen
Decorate the surface of collagen fibrils and link them to each other/other tissue components
123
Network-forming collagen
Very thin fibers that assemble into interlaced networks that formed porous sheets (basal laminae!)
Some also function as filtration barrier (kidney)
Type IV collagen is big
124
Loose connective tissues
thin colagen fibrils in sparse networks - cell densities and ground substance components, capillaries, and nerves are relatively concentrated
125
Dense connective tissue
Thick collagen fibrils more abundant than ground substance, low number ofcells
126
Collagen organization in ligaments and tendons
parallel-organized sheets
127
Collagen synthesis
- Made by CT cells
- Polypeptides synthesized on ER, post-translationally modified and assembled into a triple helix
- N and C termini are cleaved and the collagen fibrils are polymerized, with enzymes forming cross links
128
CT response to wounds
stimulation of fibroblast regulation and stimulation of ECM production
129
N-Telo peptides
Bits cleaved off collagen monomers when they are first secreted. Used as a marker of CT/bone disease in urine
130
Elastic fibers
Elastin-filamentous protein that exists in a random coil conformation that can stretch and recoil. These networks are interwoven with fibrillin that appears to organize the elastic elements
131
Hyaluronic acid
A GAG that isn't covalently attached to a protein
132
3 properties of GAG's relavent to function
1) highly negatively charged
2) Rigid extended structure causes them to readily form gels-they promote hydration of ground substance and allow diffusion of small metabolites while inhibiting movement of large structures and allows it to resist compression
3) Some can bind and inactivate other proteins (growth factors and ECM-modifying enzymes)
133
4 ECM components
1)Proteoglycans (with GAG's attached)
2)other secreted proteins/glycoproteins
inorganic and small organic 3)solutes
4)water
134
Inflammation and clotting- role of CT
1) Blood clots temporarily seal wound
| 2) CT fibroblasts and Mast cells, etc. release signaling compounds to increase inflammation
135
Inflammation processes
(i) Increase water permeability of capillary--> swelling
(ii) increase cellular permeability of endothelia to allow monocytes, lymphocytes, and other blood cells to enter C.T.
(iii) attract white cells to wound (chemotaxis)
(iv) stimulate proliferation of fibroblasts and differentiation of monocytes into macrophages
136
Histamine's effect
promote endothelial permeabilization
137
cytokines
promote inflammatory processes and go back to hematopoeitic tissue to stimulate more WBC production
138
Angiogenesis triggers after injury
macrophages secrete cytokines that promotes angiogenesis
139
Cartilage
Avascular and unable to repair in adults
140
Origin of chondrocytes
Mesenchymal stem cells
141
perichondrium
external layer of CT surrounding cartilage
142
Lacuna
Chondrocytes secrete ECM around themselves, forming lacuna
143
Hyaline Cartilage
thin, irregular collagen fibrils. Ground substance rich in proteoglycans and hyaluronic acid
(At joints and temporary during bone growth)
144
Elastic cartilage
Also contains thin collagen fibrils and proteoglycans, but distinguished by abundant elastic fibers and lamellae of elastic material
*Does not calcify*
145
Fibrocartilage
Large bundles of regularly arranged collagen that's similar to dense connective tissue (continuation of this tissue where tendons attach to bone and in intervertebral discs)
Resists compression and sheer forces
146
spongy bone
```
contains trabeculae (anastomosing spicules)
Bone marrow is between trabeculae
```
147
Bone marrow
hematopoeitic tissue or atipose cells surrounded by loose connective tissue containing blood vessels
148
Outer surface covering bone
periosteum
149
endosteum
inner surface where trabeculae contact CT
150
Osteoprogenitor cells
- generate osteoblasts and osteocytes
| - present on periosteal and endosteal surfaces and in soft connective tissue
151
osteoblasts
periosteal and endosteal surfaces where growth or remodeling occurs
secretes osteoid
Pinch off matrix vesicles that contain enzymes to initiate calcification
152
osteocytes
derived from osteoblasts
become surrounded by bone matrix and a lacuna
no cell division
extend long processes through canaliculi in the calcified matrix and form gap junctions with other osteocyte processes
153
Osteoclasts
```
derived from monocytes
resemble macrophages
degrade cartilage/bone for 3 purposes:
1)allow inward growth of blood vessels
2)remodeling
3)Ca++ store release
```
154
Bone matrix
- calcified and packed with parallel collagen
- contains glycoproteins
- contains lots of hydroxyapatite crystallized onto collagen and in the ground substance
155
Bone vascularization and innervation
-Travel through channels
| Long axis channels in long bones are called Haversian canals. Bone lamellae surround them in concentric rings
156
Osteon
Haversian canal + lamellae (concentric rings of compact bone)
157
Volkmann's canal
canals that link Haversian canals to each other and to the periosteum at the bone surface
158
Intramembranous ossification
| no pre-made cartilage
1) A group of mesenchymal cells come together in a sheet of connective tissue (condensation)
2) These mesenchymal cells differentiate into osteoprogenitors and then osteoblasts
3) This process forms "bone islands" that develop in a trabecular network
159
Flat bone formation
intramembranous ossification
160
Cartilage formation
Mesenchymal cells divide and differentiate to form chondrocytes. Chondrocytes then secrete hyaline cartilage matrix and individual chondrocytes become encased in lacunae
161
Appositional growth
Growth at the surface
162
Interstitial growth
growth from within
Early in development chondrocytes in the matrix continue to proliferate. Groups of chondrocytes that are clones derived from mitoses are "isogenous groups"
163
Epiphyseal plate
Remaining region of proliferative cartilage after birth
| aka growth plate
164
Growth of long bones
1) Chondrocytes replicate in their lacunae in the direction of the long axis of the bone and deposit hyaline matrix
2_ Osteoblasts, osteoclasts, and capillaries encroach on the cartilage from the diaphyseal side causing a continued wave of bone formation
165
Articular cartilage
The only sheath of non-proliferative cartilage left at the end of the epiphysis after bone growth
166
Growth of bone diameter
occurs on periosteum, requires continued proliferation of osteoprogenitors in the periosteum and their differentiation into osteoblasts
167
Bone resorption in adults
primarily on the endosteal surface
168
Osteoporosis
decrease in bone mass due to defects in resorption/formation coupling
169
Osteopetrosis
defective bone resorption and increased bone mass
170
Osteomalacia rickets
abnormal increases in uncalcified osteoid (interferes with mineralization
171
Matrix vesicles
Pinch off of osteoblasts and serete calcium, alkaline phosphatase, and phosphate bound to other molecules. Alkaline phosphatases are activated to form free phosphate, which precipitates with calcium to form hydroxyapatite, causes vesicle rupture, and then acts as a nucleation site
172
Short range signals that regulate bone
Bone morphogenetic proteins (BMP's)are secreted by the cell, then bind receptors and alter gene expression to control bone development and maybe other pathways
Other important pathways: FGF, Notch, Wnt
173
Other sources of Bone regulation
1) Long-range signals (steroid hormones and Ca hormones)
2) Mechanical stress
3) Neuronal stimulation
174
Parathyroid hormone and Calcium
Stimulates calcium liberation from bone
175
Calcitonin
Stiumlates calcium uptake into bone by controlling osteoblasts and osteoclasts
176
Vitamin D
important for calcium uptake from intestine
177
Tunica intima
layer of endothelial cells and a layer of elastic and loose collagenous tissues
178
Tunica media
Multiple layers of elastic laminae, smooth muscle cells, or collagen
179
Tunica adventitia
Comprised of collagenous tissue
180
vasa vasorum
blood vessels in the tunica adventitia of larger vessels
181
Pericytes
Half moon like cells that surround capillaries and may develop smooth muscle cells during vessel growth and wound healing
182
capillaries
1-2 endothelial cells surround lumen and pericytes
| All surrounded by collagenous fibrils which anchor capillary to nearby CT
183
Continuous capillaries
Endothelial cells form uninterrupted lining, transfer across lining is through pinocytotic vesicles
184
Fenestrated capillaries
Pores or fenestrations occur in endothelial cells that permit bulk flow
185
Post-capillary venules
Similar to capillaries but larger
also have pericytes
slow flow, common site of leukocyte diapedesis
endothelium is responsve to vasoregulatory substances like serotonin and histamine
186
Arteriovenous shunt
| and metarterioles
Connects larger arteries and venules
| Constriction/dilation can control whether blood flows through a capillary bed
187
End Artery
artery that supplies a section of tissue that has no alternate supply
188
Portal system
begins in a capillary bed and ends in a capillary bed
189
Pampiniform plexus
Countercurrent arrangement between artery and venous network
190
EGFR in lung cancer
dysregulation can be due to ligand overexpression, receptor overexpression, or mutation in receptor
191
EGFR treatments for lung cancer
TKI's
| Antibiodies
192
ALK gene rearrangement
3% of lung cancer
| can be targeted chemotherapeutically
193
Immunotherapy for Lung cancer
PDL1 and PD1 upregulate apoptosis when they bind. In cancer, they don't bind properly, but immunotherapy could fix this
194
Centrally located nucleus in skeletal muscle
Healing cell
195
Sarcomere boundaries
Z line to Z line
196
myofibrils
bundles of contractile muscle fibers
197
Troponin and tropomysin
Ca++ binds troponin and undergoes conformational change with tropomysin exposing a myosin binding site
198
Myosin head dynamics
Myosin is already a loaded spring when it binds actin. It does a powerstroke automatically.
ATP then reloads the spring before it binds again
199
Smooth muscle contractsion
- No troponin or tropomysin
- Calcium binds calmodulin, then ca-calmodulin binds CaM kinase, which phosphorylates myosin light chains allowing myosin to bind actin
200
Smooth muscle contraction vs. skeletal muscle contraction
- Ca++ signaling for smooth muscle is slower
- Calcium is removed by Ca pumps and Na-Ca exchangers in sarcolemma
- smooth muscle can remain in a bound state without consuming ATP
201
Mutation in Duchenne Muscular dystrophy
Dystrophin- a protein that links actin/myosin with ECM
202
titin
an enormous protein hat links myosin thick filaments to the Z-line
203
Nebulin
large protein associated with actin thin filaments thought to be important for keeping thin filaments organized
204
alpha actinin
the molecule that crosslinks actin filaments at the z-line
205
FHC mutations
Usually in cardiac myosin head
206
diffusion equation
= 6Dt,
D=diffusion coefficient
t=time
r=mean distance from starting point
207
Parvalbumin
Calcium binding protein that can bind and release calcium and diffuse faster than calcium in muscle cells
208
Myoglogin
An oxygen binding protein that is found in oxidative muscle in large quantities
209
Creatine/phosphocreatine
Molecules that replenish ATP during times of high metabolic demand
210
Transverse tubule system
Membrane structure that is basically a series of membrane invaginations throughout the muscle cell that allows AP propatagion
211
Sarcoplasmic reticulum
Each myofibril has a "stocking" of SR that stores Calcium for release
212
EC coupling
Action potential travels toward tendons and also inward into the t-system. The
membrane depolarization in the t-system is translated into Ca+2 release from the SR
213
T-tubule/SR coupling
DHPR in the T-tubule is a complex of several subunits, one is a vg Ca++ channel
RyR is in the SR membrane
A conformational change in DHPR causes RyR receptor to open and flood the cell with calcium
214
Malignant hyperthermia
abnormal SR calcium release channel causes catastrophic rise in temperature when given certain volatile anesthetics
215
Treatment of malignant hyperthermia
dantrolene injection --> blocks Ca++ release from SR
216
DHP receptor mutation
causes muscular dysgenesis --> embryonic lethal
Gene therapy might be possible
Cardiac DHP is coded by a different gene
217
Difference between cardiac and skeletal muscle EC coupling
Ca2+ entry is required to trigger ca++ release by the SR receptor because it has a Ca++ binding site
218
Gap junctions in muscle
Couple both smooth and cardiac muscle cells, but not skeletal muscle skells
219
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.
220
Grading tension in cardiac and smooth muscle
both respond to NT's and hormone-like molecules
221
satellite cells
stem cells that are source for new myoblasts to repair injured muscle
222
Signalling molecules for satellite cells
Fibroblast growth factor, insulin growth factor, hepatocyte growth factor, NFkappaB, NO, myostatin (promotes muscle cell degradation), LIF ( promotes satellite cell proliferation
223
fibroblasts and satellite cells
Fibroblasts interact with satellite cells to influence which cell types will be produced
224
Repair of cardiac muscle
doesn't really happen. There aren't satellite cells and mostly fibroblasts just make scar tissue
225
Smooth muscle repair
Smooth muscle cells can dedifferentiate, enter mitosis, and regenerate smooth muscle cells (this might be related to how good they are at proliferating)
226
Metabolic muscle fatigue
primarily an increase in inorganic
phosphate and a decrease in pH (from 7 to 6.5) that lead to decreased ca++ release. ATP levels change very little, but phosphocreatine levels are depleted
227
Duchenne Muscular dystrophy common clinical features
cardiomyopathy!!
High creatine kinase
toe walking
Gower's sign
228
Treatment of DMD
Corticosteroids
229
Myostatin
Muscle growth inhibitor
Potential treatment for DMD=inhibit myostatin!
May be involved in muscle wasting in AIDS patients
230
Clinical signs of malignant hyperthemria
***Masseter spasms***
Increased CO2 production
Rhabdomyolysis (muscle breakdown)
231
Tests for Malignant Hyperthermia
Halothane/caffeine test
232
anesthesia's that are deadly in malignant hyperthermia
Halothane and succinylcholine
233
Hypertrophic Cardiomyopathy
***myocyte disarray
fibrosis-->arrhythmia
dysplastic intramyochardial arterioles--> ischemia
234
Endomysium
Surrounds myocytes
235
perimysium
surrounds muscle fascicules
236
epimysium
surrounds entire muscles
237
Clinical presentations of Hypertrophic cardiomyopathy
1) murmur if LV outflow is obstructed
2) Pump failure (dyspnea, angina)
3) arrhythmia (syncope/sudden death)
4) Sports/family screening
238
Potential Hypertrophic cardiomyopathy cure
Rnai
239
Genetic cause of malignant hyperthermia
mutation in RyR, they stay chronically open when people are given triggering antibiotics
