KIN 406 Flashcards
4 functions of muscle?
Generate force, fuel storage, temperature regulation, force absorber
3 fuels in muscle
Glycogen, fat (lipid droplets), and protein
Why is it important to study mechanisms?
Better outcomes because specific things can be treated and less negative effects because specific things are treated
Is muscle a homogenous tissue?
NO. It is heterogeneous. No 2 fibres are the same because they all differ in neural input, MHC form, enzymes, proteins, etc.
Contractile proteins?
Actin and myosin
Regulatory proteins?
Troponin and Tropomyosin
Role of SR?
storage, release (RyR receptors), and uptake (SERCA) of Ca2+
Responsible for weak to strong binding?
Release of Pi
Responsible for power stroke?
Release of ADP
Responsible for detachment of myosin from actin?
ATP binding
Why are muscle cells multi-nucleated?
Ability to regenerate and ability to adapt and be eliminated to physciological and environmental stimuli
Muscle cell = ?
Muscle fibre or myocyte
Cell membrane = plasma membrane = ?
Sarcolemma
Cytoplasm = ?
Sarcoplasm
What does the sarcoplasm contain?
All portions of the cell that are not membrane or nucleus
What does the cytosol contain?
The fluid portion of the cell (does NOT contain cell membrane, organelles, or nucleus)
Endoplasmic reticulum = ?
Sarcoplasmic reticulum
Organization of a skeletal muscle?
Muscle > fasicles > fibres > myofibrils > thick/thin filaments > sarcomeres
Triad of the reticulum?
2 terminal cisternae and 1 transverse tubule
Cytoskeleton proteins?
Titin (elastic and helps arrange thick filaments) and Nebulim (not elastic, helps arrange thin filaments)
Components of myosin molecule?
2 heads each with 1 heavy chain and 2 light chains (alkali and phosphorylable)
Why does muscle damage cause a significant loss in force?
Shape of sarcomere is alters = less cross bridges can form = less force production
What causes the contraction and relaxation of a muscle?
Changing the voltage across the membrane via sodium and potassium
What is the role of the Na+/K+ ATPase?
Controls cell volume and maintains the Na+ /K+ gradient across the cell membrane
What is the main cause of relaxation in muscle?
The neural signal stops, so the DHPR are no longer tripping of the Ry receptors on the SR, so calcium release ceases, and SERCA uptakes calcium, causing it do dissociate from TN-C, allowing TM to slide back into its blocking position, thus stopping muscle contraction
Two parts of the SR?
Terminal cisternae and the longitudincal SR
Role of the terminal cisternae?
Forms junction with T-tubule called triad membrane, contains Ca2+ release channel, most Ca2+ is bound to calsequestrin, major function is Ca2+ release
What is the role of the longitudinal SR?
Contain the CA2+ ATPase pumps (SERCA), major function is Ca2+ uptake
Primary factor that differentiates muscle or muscle fibre types?
The rate/speed of contraction
What determines Vmax, and therefore fibre type?
Myosin heavy chain
Myosin heavy chain forms from slowest to fastest?
Type I < Type IIa < Type IIx(d) < Type IIB
Do humans have Type IIb fibres?
NOOOO, only rodents
Why does a Type II fibre have a shorter twitch than a Type I fibre?
It has much faster calcium release (RyR-1 Fast), and much faster Ca2+ uptake due to more SERCA and a faster isoform of SERCA (SERCA 1)
Do humans have just one kind of muscle fibre?
NO, need the 50-50 split so we can perform a variety of activities
Why is the epxression of fibre type different throughout a muscle?
Because it is multinucleated, so there is different expression of myosin heavy chains throughout the muscle
Other factors, aside from MHC, that can differentiate muscles?
Fatigue characteristics, metabolic characteristics, and morphological characteristics
Fibres that fatigue the fastest? The slowest?
Type II is fastest. Type I is slowest.
How are the metabolic characteristics of a muscle measured?
Measure enzyme activities of representative pathways
Fast-glycolytic fibres? Fast oxidative-glycolytic_ Slow-oxidative?
Type IIx/b, Typpe IIa, Type I
Fibre type with a bigger diameter?
Type II
Fibre type with more SR?
Type II
Fibre type with more mitochondria?
Type I
Smallest amount of a muscle that can be activated?
Motor unit
Ways to increase force in a muscle?
recruit more motor units and increase the frequency of firing to the motor units to have summation
What is a motor unit?
The motor neuron and the muscle fibres it innervates
Why is the loss of MNs in a diseased state a problem?
Fibres are re-innervated by other MN, causing an increase in the size of the motor unit, which decreases the control of force
The fewer the number of fibres per motor unit, the…?
Finer the control of force because there are more steps involved until summation is reached
What type of motor units are recruited first?
Type I motor units are recruited first because they won’t fatigue as fast
What are the differences in force in a motor unit attributed to?
The differences in the number of fibres per motor unit
What type of motor unit produces the most force?
Type IIB FF
Fibre type transformation sequence?
IIb IIbx IIx IIa IIc Ic I
Most oxidative fibre in rats? In humans?
IIa in rats, and I in humans
3 energy delivry systems in muscle?
HEPT, glycolysis, and oxidative phosphorylation
HEPT?
Transfer of a phosphate group to ADP to make ATP, doesn’t involve O2, VERY fast (high power), but can only last approx. 10 s (low capacity)
Glycolysis?
Degradation of glucose or glycogen (glycogenolysis), does not involve O2, 11-12 reactions in cytosol
Power of anaerobic glycolysis?
Medium/high power because the large amount of ATP that be generated per unit time, due to hte high activity of enzymes in this pathway
Why can’t you rely heavily on glycolysis for a long time?
- availability of substrates (i/e/ muscle glycogen) 2. Build up of lactic acid (H+ causes acidosis)
Capacity of glycolysis for producing ATP?
Moderate capacity
Enzyme that converts glyocgen to G-1-P?
phosphorylase
Enzyme that takes glucose to G-1-P?
hexokinase
Energy investment for glycogen? Glucose?
1 ATP, 2 ATP
Capacity of aerobic metabolism?
Larage capacity because of large fa and glycogen stores (liver and muscle)
Power of aerobic metabolism?
Low-moderate power because the rate of ATP regeneration is fairly low and is limited by O2
Oxidative phosphorylation?
The formation of ATP from ADP and Pi in association with electron transfer from fuel substrates to coenzymes to oxygen
Krebs cycle?
completes the oxidation of substrates and produces NADH and FADH2 to enter the ETC
ETC?
oxidative phosphorylation, electrons removed from NADH and FADH2 are passed along a series of carriers to produce ATP, H+ from NADH and FADH2 are accepted by O2 to form water.
3 stages of oxidative phosphorylation?
- formation of acetyl-CoA from CHO (pyruvate), fats (fatty acids), or amino acids (proteins) 2. oxidation of acetly groups in Krebs cycle to form NADH and FADH2 3. Oxidation of NADH and FADH2 in ETC to form ATP from ADP and Pi
Skeletal muscle is derived from what type of cells, and where are they found?
Derived from myogenic stem cells found in the embryonic mesoderm
At what point in gestation do mesodermal stem cells migrate to their appropriate site and differentiate into myoblasts?
At 6 weeks gestation
What do the large majority of myoblasts become?
They aggregate and fuse to form multinucleated myotubes (primary myotube) The myoblast plasma membranes fuse, and form a central chain of nuclei.
What does some myoblasts remain as?
2-5% remain as a single cell with mitotic potential…aka satellite cells found in fully differentiated muscles
At what point in muscle development do cells lose their mitotic potential?
After myoblasts are formed
Why does it make sense that muscle cells cannot undergo mitotsis once myoblasts are formed?
Muscle fibres are very long, making it difficult from an engineering standpoint to allow for replication. Also, if the cells were actively dividing, it would decreae force production because the hexagonal shape of the sarcomeres needed for contraction would be altered.
What type of myotubes can independently form a muscle fibre?
Primary
How do secondary myotubes become their own fibres?
The additional myoblasts aggregate on the primary myotube and form a secondary myotube.These secondary myotubes will also become independent fibres with their own basement membrane. Early during development, though, both the primary and secondary myotubes are contained within the same basement membrane.
Primary myotubes are suggested to form what type of muscle?
Slow muscle (soleus)
Secondary myotubes are suggested to form what type of muscle>
Fast (EDL)
In what week of gestation in humans are most muscle groups well defined?
7-9th week
At what time of gestation does the synthesis of contractile protein (actin and myosin) begin and the first signs of cross-striation appear?
7th-9th week. Up until then there was no contractile proteins because there was no contraction or innervation…myogenic stem cells and myoblasts have no actin or myosin.
How does the transition from myoblast to myotube occur>
Upregulation in the epressions of important muscle specific transcription facots (Myf genes,,,Myf-5, MyoD, myogenin)
What are the Myf genes, what do they do?
Myogenic factor 5 (Myf-5), myogenic determination (myoD), and myogenin. Promote myoblast proliferation and differentiation.
If Myf genes are overexpressed in non-myogenic cells (e.g. fibroblasts) whay happens?
The cells will form muscle
Once myotubes are formed, proliferation and differentiation are blocked by?
Myostatin and inhibitor of differentiation proteins (Id)
How does myostatin and Id protein primarily work?
Through the inhibition of MyoD
What doe MyoD/Myf-5 mice lack, but what do they have?
They lack skeletal muscle development (no actin, myosin, desmin, etc), but they do still develop smooth muscle.
From what week of gestation on do myofibrils proliferate leading to hypertrophy of the muscle fibre?
11 weeks onward. At his stage, there are increases in girth, but also increases in length by the addition of sarcomeres at each end
At what week of gesetation are all myotubes enclosed in the basement membrane?
16 weeks
At what weeks of gestation do all the nuclei of hte myotubes (primary and secondary) move to the periphery of the fiber?
18-23 weeks
At what week of gestation are muscle fibres in each human set?
24 weeks
What form of myosin to embryonic and fetuses express?
Type IIC
What type of MHC do Type IIC fibres express>
Both Type I and Type IIa, which will allow the fibres to develop into Type I or Type II muscle
WHen is the fetal form of myosin replaced by the adult myosin?
Once the muscle starts contracting, following innervation
Approximate number of nuclei per mm of muscle length?
100-200 nuclei
The number of nuclei is positively correlated to what?
Fiber size…larger fibres have more nuclei and smaller fibres have less nuclei
The greater the number of nuclei, the greater the…
protein production