Muscle Contraction Flashcards
1
Q
- What are T-Tubules in myofibrils extensions of?
- What is their function?
A
- extensions of plasma membrane (sarcolema)
- a tubular invagination of the sarcolemma of skeletal muscle fibers that surrounds myofibrils as the intermediate element of the triad in skeletal muscle
- Function:
- involved in transmitting the action potential from the sarcolemma to the interior of the myofibril.
2
Q
In skeletal muscle, what makes up the triad?
A
1 t-tubule and 2 terminal cisternae
3
Q
- What are the 7 steps of muscle contraction in a myofibril?
- Which bands are shortened?
- Which bands stay the same length?
A
- Depolarization of motor end plate (via Na+ channels) travels along muscle cell and down T-tubule
- Depolarization of the voltage sensitive dihydropyridine receptor, mechanically coupled to the ryanodine receptor on the SR
- induces a conformational change in both receptors, causing Ca2+ release from sarcoplasmic reticulum.
- Release Ca2+ binds to troponin C, causing a conformational change that moves tropomyosin out of myosin binding groove on actin filaments
- Myosin releases ADP and Pi—-> displacement of myosin on the actin filament (power stroke)
- contraction results in shortening of the H and I bands between the Z lines
- A band remains the same length
- Binding of new ATP molecule causes detachment of myosin head from actin filament
- hydrolysis of bound ATP—> ADP causes myosin head to adopt high energy position (“cocked”) for the next contraction cycle
4
Q
What are two main differences between skeletal and smooth muscle?
A
- Skeletal:
- nucleus located peripherally
- multiple nuclei per cell
- Smooth muscle
- nucleus located centrally
- one nuclei per cell
5
Q
- What is a sarcomere?
- What is it a component of?
A
- Myofilament
- area between 2 Z lines
- composed of thin (actin) and thick (myosin) filaments
6
Q
Components of Myofilament:
- A band
- I band
- H band
- M line
- Z line
What are they made of? How do they change (or not) shape?
A
-
A band:
- “dark” part of skeletal muscle straitions
- remain constant in width
- composed of all of myosin (thick) and some actin (thin)
-
I band:
- “light” part of skeletal muscle straition
- Composed only of thin filaments (actin)
- Changes in size (smaller with contraction)
- H band:
- bisects A band (1/2)
- composed only of thick filament (myosin)
- changes in size (smaller with contraction)
-
M line:
- bisects the H band
- attachment site of thick filament (myosin)
-
Z line:
- dark lines that bisect I bands
- attachment site of thin filaments
- separates each sarcomere
7
Q
- Function of terminal cisternae?
- What are they a part of?
A
- Terminal cisternae are enlarged areas of the sarcoplasmic reticulum surrounding the transverse tubules.
- make up triad (with t-tubule)
-
Function:
-
store calcium
- (increasing the capacity of the sarcoplasmic reticulum to release calcium)
- release it when an action potential courses down the transverse tubules, eliciting muscle contraction.
-
store calcium
8
Q
Definitions of:
- Sarcolemma
- Sarcoplasm
- Sarcoplasmic Reticulum
- Myofibrils
- Myofilaments
- Sarcomeres
A
-
Sarcolemma
- plasma membrane of skeletal muscle cell
-
Sarcoplasm
- cytoplasm
-
Sarcoplasmic Reticulum
- endoplasmic reticulum
-
Myofibrils
- cylindrical organelles found inside skeletal muscle cells
-
Myofilaments
- filaments of a myofibril
- organized into repeating units called sarcomeres
-
Sarcomeres
- regions between two successive Z lines
9
Q
What is the rate limiting step of Synaptic Transmission at the neuromuscular junction?
A
- Ca2+ diffusion into and through the axon terminal to the snare proteins
10
Q
What are the 3 main SNARE proteins and what are they attached to?
A
- Synaptobrevin (v-SNARE)
- attached to vesicles
- Syntaxin and SNAP 25 (t-SNARE)
- attached to presynaptic membrane
-
Synaptotagmin
- Ca2+ sensor that triggers the actual fusion event
- makes other SNARE proteins twist together to pull vesicle down for fusion and exocytosis
- Ca2+ sensor that triggers the actual fusion event
11
Q
- What 2 things make up choline acyltransferase (ACh)?
- Enzyme?
- Where is it made?
A
- ACh= Choline + Acetyl CoA (from Kreb’s cycle)
- via choline acetyltransferase
-
Made in:
- cystoli neuron soma (body) and transferred to axon terminal
12
Q
ACh remains in synaptic space for very short time (ms)
- What is ACh broken down into?
- enzyme?
- where does this happen?
A
-
broken down into:
- acetate: diffuse out
- choline: always recycled
- via acetylcholinesterase
- in synaptic cleft
13
Q
- How does ACh get from the Soma to the NMJ?
- proteins
- types of transport?
A
-
Kinesin (to axon from cell body)
- fast or slow anterograde
-
Dynein (from soma to axon)
- fast retrograde
- Microtubules
14
Q
- What types of channels are ACh (nicotinic)?
- What mostly enters?
A
-
nonselective cation channels: Na+, Ca2+, K+
- Na+ wants to move inside due to [] gradient and electrical gradient
- K+ wants to move outside but is attracted to the (-) charge inside cell so it gets stuck
- Ca2+ doesn’t move in as much because it is larger (2+ charges)
15
Q
- How many subunits does the ACh receptor (nicotinic) have?
- how many ACh need to bind to open the channel?
A
- 5 subunits
- need 2 ACh to open
16
Q
What is the function of Ca in the presynaptic membrane of NMJ?
A
- AP in nerve terminal open Ca2+ channel
- Ca 2+ entry causes SNARE proteins to interact and fusion of vesicles for exocytosis
17
Q
- What is the pathological mechanism of Myasthenia Gravis?
- What is the clinical presentation?
- symptoms?
- What is it associated with?
A
-
Pathology: Autoimmune
- B lymphocytes produce antibodies that bind AChRs, blocking ACh binding sides
-
Clinical presentation:
- muscular weakness that gets worse during activity
-
Symptoms:
- double vision
- drooping eyelids
- slurred speech
- dysphagia
-
Associated with:
- thymic hyperplasia or thymoma
18
Q
What are the three main mechanisms in which antibody binding causes Myasthenia Gravis?
A
- Less extensive junction folds (less SA), widened synaptic cleft (takes longer time and more chance of diffusion) and less AChR’s
- Antibody binding causes crosslinking of individual receptor by tagging them for degradation
- receptor turnover rate increase by 3
- B lymphocytes produce antibodies that bind AChR’s, blocking ACh binding sites
19
Q
- What is the pathology of Lambert Eaton Myasthenic Syndrome?
- How does it present?
- Paraneoplastic syndrome?
A
-
Pathology:
- antibodies against presynaptic (P/Q type) Ca2+ channels at NMJ
-
Clinical presentation:
- musuclar weakness (proximal arms and legs) that improves with activity
- eyes are usually spared (different than MG)
- musuclar weakness (proximal arms and legs) that improves with activity
-
Paraneoplastic syndrome:
- small cell cancer of the lung
20
Q
Myasthenia Gravis vs. Lambert Easton Myasthenic Syndrome?
- effect of cholinesterase activity
- neurotransmission with repetitive stimulation
- mainly affects where on body?
- effect of activity on muscular weakness?
- associated with which cancers?
A
-
Myasthenia Gravis: (post synaptic)
- AChR agonists and acetylcholinesterase inhibitors helpful
- reduced neurotransmission with repetitive stimulation
- characteristic eye droop
- muscular weakness gets worse with increased activity
- associated with Thymic hyperplasia or Thymoma
-
Lambert-Eaton Myasthenic Syndrome: (presynaptic)
- Anti-cholinesterase therapy is less effective
- not enough ACh to begin with
- Enhanced neurotransmission with repetitive stimulation
- strongest affect seen in proximal limbs
- no eye effects
- muscular weakness improves with activity and exercise
- associated with small cell carcinoma of lung
- Anti-cholinesterase therapy is less effective
21
Q
In cross bridge cycle in muscle contraction:
- what moves the myosin head?
- what releases myosin from actin?
A
- ATP binding releases myosin from actin
- ATP hydrolysis move myosin head
22
Q
- How are actin filaments attached to Z lines?
- What attaches Z and M line proteins?
A
- Actin filaments attach to Z line by alpha-actinin
-
Titin attaches Z and M line proteins
- “springy”, recoils to restore length of sarcomere at relaxation
23
Q
What is the function of Desmin, Ankyrin and Dystrophin in myofilament?
A
-
Desmin and Ankyrin:
- connect Z line to membrane
-
Dystrophin
- connect actin to membrane at dystroglycan-sarcoglycan complex
24
Q
What does smooth muscle have instead of troponins?
A
- Calmodulin
- binding of 4 Ca2+ ions cause change in conformation and allows actin and myosin to bind
25
Q
What are the 2 sources of Ca2+ in smooth muscles?
A
-
Unlike skeletal muscle, smooth muscle is dependent on two sources of calcium in order to initiate contraction.
- These two sources are:
- calcium sequestered in the S.R. of the smooth muscle cell.
- extracellular calcium that can enter the smooth muscle cell via calcium channels on the membrane of the smooth muscle cell.
26
Q
- Role of myosin light chain kinase activity in smooth muscle contraction?
- Role in relaxation?
A
-
Contraction:
- Myosin light chain kinase (MLCK) is an enzyme that phosphorylates one of the two myosin light chains associated with the myosin head.
- The MLCK hydrolyzes ATP and takes the inorganic phosphate (Pi) from the ATP and puts it on the myosin light chain.
- Once the myosin light chain is phosphorylated, the myosin head develops a high affinity for the actin active site and binds readily to it.
- Myosin light chain kinase (MLCK) is an enzyme that phosphorylates one of the two myosin light chains associated with the myosin head.
-
Relaxation:
- the myosin light chain that was phosphorylated by the MLCK must be dephosphorylated by the myosin light chain phosphatase mentioned previously.
- Once the myosin light chain is dephosphorylated, the myosin head no longer has significant affinity for the actin active site and relaxation ensues.
