Lecture 21 & 22: Muscles I & II Flashcards
Describe the composition of a muscle fiber.
Myofibrils covered by a cell membrane called the sarcolemma
What are T-tubules?
Invaginations of the sarcolemma
What is the terminal cisternae of the sarcoplasmic reticulum?
Part of the SR near the T-tubules
What is the sarcoplasmic reticulum? How is calcium bound inside?
ER of the muscle cells containing high calcium bound by calsequestrin (to keep concentration high in SR)
What triad is important for excitation contraction coupling?
2 terminal SR cisternae + 1 T-tubule
Describe the Na+ and K+ channels along the sarcolemma and its T-tubules.
They are all over the sarcolemma including down the T-tubules, but due to the limited spaces in the T-tubules the K+ is unable to clear during repolarization which temporarily inhibits repolarization and prevents hyperpolarization
What is the intracellular [K+] in muscle cells? Why?
It’s elevated because the due to the limited spaces in the T-tubules the K+ is unable to clear during repolarization
What helps compensate for the difficulty of the K+ to exit muscle cells during repolarization? How does this affect the RMP of muscle cells?
Leakage Cl- channels which are constantly active: lower RMP (-85/-90 mV)
Why is there no undershoot in repolarization of muscle cells?
Because of the accumulation of K+ in the T-tubules
Explains muscle fatigue? How can it be compensated for?
Caused by increase in extracellular K+ (making it harder for cells to repolarize) Lactic acid boosts Cl- leakage channels (allowing for repolarization)
What is myotonia?
Cl- leakage channels are defective
What is excitation-contraction coupling?
Process by which the AP in skeletal muscle causes calcium release from the SR to the intracellular space of the muscle fiber generates force (mechanical contraction)
What is the difference between excitation secretion coupling and excitation contraction coupling in skeletal muscle?
Excitation secretion coupling: happens in pre synaptic neuron and requires extracellular calcium Excitation contraction coupling: happens in the muscle cells and does not require extracellular calcium
Does excitation contraction coupling require EXTRACELLULAR calcium? Why?
Skeletal muscles: no (BUT the ryanodine receptor still needs to be activated) - because we’ve evolved to be able to react fast Smooth and cardia muscles: yes
What are the 2 important parts of the triad for excitation contraction coupling? Where is each located?
2 calcium channels to release calcium: 1. L-type channel = DHP receptor on T-tubule 2. Ryanodine receptor = calcium-release channel on SR (activated by calcium or activated DHP) THEY ARE CONNECTED
Describe the 3 steps of excitation contraction coupling. Is this pathway essential in skeletal muscle? How fast is it?
- Membrane depolarization causes L-type channel DHP receptor to be activated = conformational change 2. Mechanical coupling between L-type (ligand) and ryanodine receptor acitvation 3. Calcium exits the SR into the sarcoplasm and activates troponin C, leading to muscle contraction 4. Ca-ATPase on the SR pumps calcium back into SR
How can contraction happen with extracellular calcium coming into the sarcoplasm (in skeletal muscle)?
- Depolarization and activation of DHP receptors 2. Flow of extracellular calcium into sarcoplasm through DHP 4. Ryanodine receptors activated 5. Release of SR calcium into sarcoplasm
List the 15 steps to achieve muscle contraction in skeletal muscle.
- Terminal end of motor neuron takes up calcium after depolarization 2. ACh exocytosed 3. AChRs bind ACh in muscle fiber and produce EPP 4. EPP triggers AP and a depolarization wave is sent along the sarcolemma, down the T-tubules into the triads 5. Depolarization reaches DHP receptor and activates it 6. DHP activates ryanodine receptors 7. Calcium is released into sarcoplasm 8. Myosin hydrolyzes ATP recocking the myosin head for it to be perpendicular to actin = cross bridge release 9. Calcium binds to troponin (attached to tropomyosin) 10. Shift in tropomyosin= exposure of myosin binding sites on actin 11. Myosin (bound to ADP + Pi) binds to actin 12. Myosin releases ADP + Pi = contraction (crawling on actin filaments) 13. ATP binds to myosin= actin release 14. Calcium is resorbed by SR by Ca-ATPase 15. Tropomyosin hides myosin binding sites on actin = muscle relaxation
Skeletal muscle: multi or uninucleated?
Multi
What is the A band of the sarcomere?
Thick filaments in their entirety
What is the M line in the sarcomere?
Cuts the thick filaments in half
What is the I band of the sarcomere?
Thin filaments ONLY
What is the H zone of the sarcomere?
Thick filaments ONLY
Describe the sarcomere composition in skeletal muscle.
Thin filaments: actin, tropomyosin, and troponin Thick filaments: myosin
What part of the sarcomere moves during muscle contraction?
Thin filaments
What is the Z-line of the sarcomere?
Cuts the thin filaments in half (also where invagination of T-tubules occurs)
Describe the thin filaments in the sarcomere in skeletal muscle.
Two filamentous actin fibers of individual globular actin monomers intertwine. Attached at regulatory points is tropomyosin which hides the myosin binding sites. Troponin is attached at the ends of tropomyosin and can bind calcium.
What are the 3 subunits of troponin?
- Troponin T: tropomyosin binding site 2. Troponin I: locks tropomyosin in place to hide myosin binding sites on actin 3. Troponin C: 4 calcium binding sites: 2 low affinity and 2 high affinity (bound at all times)
Describe the thick filaments in the sarcomere. What do they allow?
2 chains of light meromyosin + 2 heads of heavy meromyosin (bind actin and ATPase) + 2 hinged regions Both connected by hinged regiond that allow the cross bridge to bend 45 degrees with respect to the backbone allowing for the cross bridge movement
How big is the angle motion of the myosin head?
45 degrees
How does ATP affect myosin’s affinity for actin?
ATP decreases its affinity for actin
By how much does the sarcomere shorten during contraction?
1 microm
What does the speed of the cross bridge cycle depend on? What is this theory called?
The speed of the ATPase on the myosin head The sliding filament theory
What does the strength of the cross bridge cycle depend on?
The amount of cross-bridges formed, which depends on the amount of calcium present
What happens if calcium concentration stays high in a muscle cell?
Cell death
What happens in rigor mortis?
Lack of ATP keeps myosin from unbinding actin so the muscles remain contracted without any action potential involved
What are the 3 major sources of ATP? Explain each one and how it potentially affects the cellular environment.
- Glycolysis: glycogen broken down by phosphorylase (myophosphorylase in muscles): cell acidosis because of lactic acid 2. Krebs cycle (oxidative phosphorylation) burning fatty acids with water and CO2 as byproducts (easily diffusible so no side effect) 3. Creatine phosphate: very low capacity emergency storafe
What are the 2 times ATP is used during muscle contraction?
- To dissociate myosin from actin 2. To remove calcium from sarcoplasm back into SR
Are the invaginations created by the T-tubules extracellular or intracellular?
Extracellular
How is maximal force (tension) of contraction of a sarcomere achieved?
Maximal overlap between actin and myosin to allow for maximal number of cross-bridges
What is contraction strength dependent on?
The number of cross-bridges
What is the resting length of the sarcomere?
The optimum position of myosin relative to actin
Would small deviations in sarcomere length affect strength of contraction? Why?
No because the resting length of the sarcomere is the optimum position of myosin relative to actin
How is the force of contraction controlled in cardiac muscle?
By altering the resting muscle length
What is the purpose of the T-tubules?
Plasma membrane wants to make sure the AP goes deep in the muscle cell to cause a contraction
What is special about the DHP receptor on skeletal muscle membranes not needing calcium entry for contraction?
Only place in physiology where ion flow is not required through an ion channel for activation
What is the hierarchy of the skeletal muscle?
Actin+myosin > sarcomeres in series > myofibril > myofiber > muscle bundle > muscle
What are the potassium, sodium, and calcium concentrations of the SR (high/low)?
K: High Na: Low Ca: High
What are the potassium, sodium, and calcium concentrations of the T-tubules (high/low)?
K: Low Na: High Ca: High
What are the potassium, sodium, and calcium concentrations of the sarcoplasm (high/low)?
K: High Na: Low Ca: Low
Which step is ATP dependent in excitation-contraction coupling?
The action of Ca-ATPase to pump Ca back into the SR
What does it mean for the RMP if [K+] out is higher than normal?
RMP is depolarized
Myofiber: poly or uninucleated?
Poly
Does the A band change in length?
No
Does the I band change in length?
Yes: shrinks
Which 2 proteins make stripes on striated muscles?
Actin and myosin
Which 2 proteins in skeletal muscle are the regulatory ones? What do they form?
Tropomyosin and troponin = regulatory protein complex
What distinguishes the red and white muscles?
Different types of myosin based on the speed of their myosin ATPase (and their myoglobin content): white: fast and red: slow
How many heads on myosin?
2
What does the number of cross bridges cycling depend on?
Calcium concentration
What causes cramps?
ATP not attaching to myosin so that it releases actin so the muscles remain contracted
What does the curve of intracellular [Ca] vs the force of the ATPase activity on myosin look like? Why?
Sigmoidal because it takes a certain amount of calcium to expose myosin binding sites on actin (slow start) and then it goes fast and then it reaches a plateau
At what intracellular [Ca] is contraction maximal?
10 microM
What is the minimal intracellular [Ca] for contraction?
100 nM
How can you measure the force of contraction biochemically?
ATPase activity
What is relaxation of skeletal muscle after a contraction controlled by?
The uptake of calcium by the SR Ca-ATPase
What “charges” the power stroke?
Hydrolysis of ATP
“The cell has a larger resting potential”: what does this mean?
MORE NEGATIVE RMP!
What would be the effect on the RPM if the plasma concentration of K+ was lower than normal (but same inside the cell)?
RPM would be hyperpolarized = larger
What is different about the action potential of a skeletal muscle cell instead of a nerve? Why? 3 things.
- There is a hump during the repolarization because the K+ is getting stuck in the T-tubules and so the Cl- leakage channels will be driven by the positive charge and take over to help repolarize 2. No undershoot 3. RMP is lower in muscle cells
What does the maximum velocity of the shortening of the cross-bridge depend on?
Type of ATPase: fast and slow
What does the maximum tension of the cross-bridge depend on?
The degree of overlap of the cross-bridge
What is 1 cross-bridge?
The attachment of myosin with actin within the muscle cell
What is an isometric contraction? 2 examples?
The muscle tension developed is less than its opposite load so it generates force without changing the length of the muscle. The muscle cannot change from a prefixed length but the tone changes. For example you are pushing against a wall or muscles pulling on tendons
What is an isotonic contraction? Example? 2 types?
Generates force by changing the length of the muscle meaning the muscle tension developed is greater than its opposing load (lifting). The muscle tone (strength) therefore remains the same, but the length changes. For example Kate lifting hamsters (that are a constant weight) at the gym. My muscles will not change their strength but I will decrease the length of my muscles as I move the hamsters up and down. Two types of isotonic contraction: i. Concentric- muscle shortening ii. Eccentric- muscle lengthening
What is a tetany? What is it responsible for?
The muscle response to multiple APs at high frequency to generate a greater force of contraction due to the fact that the calcium does not have time to be reuptake into the SR Responsible fora high, sustained maximal force
What is the shortening velocity of an isotonic contraction dependent on?
Inversely proportional to the magnitude of the load
Are heart muscles cells performing isometric or isotonic contractions?
Isotonic contractions
With what types of contractions is the force-velocity relationship shown? What do they show?
Isotonic contractions They show that as the load decreases, the contraction velocity increases
What type of muscle contractions are movements made of?
First isometric and then isotonic when the load is greater than the tension