Midterm Review Slides Flashcards
What are the 4 general types of cellular movement?
- reorganization of the cytoskeletal network – growth of the cytoskeleton in one region of the cell pushes the cell membrane outward (amoeboid movement)
- motor protons ‘walk’ along relatively fixed elements of the cytoskeleton (can be used for cargo transport throughout the cell)
- motor proteins attached to the cell membrane (fixed) pull on the skeleton, moving an element of the cytoskeleton
- motor proteins and cytoskeleton are arranged such that they slide over each other, pulling the cell into a different shape
What are microtubules?
long hollow tubes composed of repeating units of tubulin (which is a dimer of alpha-tubulin and beta-tubulin)
How do microtubules grow and shrink?
- grow by adding tubulin dimers on the (+) end
- shrink by shedding tubulin dimers on the (-) end
What is the main factor that influences the rate of growth and the rate of shrinkage in microtubules?
concentration of tubulin (Cc)
- microtubule grows if the concentration of tubulin is greater than Cc
- microtubule shrinks if the concentration of tubulin is less than Cc
- Cc is lower for the (+) end of the microtubule compared to the (-) end
Where is the microtubule-organizing centre (MTOC)?
near the nucleus
Where is each end of a microtubule relative to the microtubule-organizing centre (MTOC)?
- (-) end is located at the MTOC
- (+) end extends out toward the cell membrane
Which motor proteins are associated with microtubules?
- kinesin
- dynesin
In what direction along the microtubule does kinesin and dynein move in?
polarity of the microtubule sets the direction of movement
- kinesin moves towards the (+) end
- dynein moves towards the (-) end
What are microfilaments?
long strands of the globular protein beta-actin (G-actin)
- G-actin polymerizes to form F-actin
How does the growth of F-actin (microfilaments) compare to microtubules?
similar to microtubules
- spontaneous growth
- has polarity
How does actin growth occur?
- capping protein on (-) end of F-actin to prevent shrinking
- growth at (+) end of F-actin (addition of G-actin monomers)
How does actin treadmilling occur?
- growth at (+) end of F-actin
- shrinkage at (-) end of F-actin
- a given G-actin monomer will move from the (+) to (-) end of actin
What is actin polymerization important for?
- amoeboid movement
- cell movement
What motor protein is associated with microfilaments?
myosin (many different types)
How might microfilaments and myosin work together to generate cellular movement?
- microfilaments act as tracks along which myosin moves (important for intracellular transport)
- myosin can pull on filaments
What is the function of myosin V?
recall myosin V moves towards the (+) end of actin filaments – towards the plasma membrane
- intracellular transport (cargo)
In what direction does myosin move along microfilaments?
- most known types of myosin move towards the (+) end
- EXCEPTION: myosin VI moves towards the (-) end
What are the functions of myosin VI?
recall myosin VI moves towards the (-) end of actin filaments – towards the nucleus
- intracellular transport (cargo)
- endocytosis
Sliding Filament Model
What are the stages of the cross-bridge cycle?
- ATP binds to myosin, causing myosin to detach from actin
- releasing actin causes myosin to hydrolyze ATP into ADP and Pi (which remain bound by myosin)
- ATP hydrolysis causes myosin to extend and attach to actin (forms a cross-bridge)
- release of phosphate promotes the power stroke
- ADP is released
Sliding Filament Model
What is unitary displacement?
the distance that myosin steps during each cross-bridge cycle
- this keeps them on track, and avoids interference with other things
Sliding Filament Model
What is the unitary displacement for myosin monomers?
variable
Sliding Filament Model
What is the unitary displacement for myosin dimers?
dependent on the periodicity of the actin filament
- ie. myosin V ‘walks’ along a microfilament with ~36 nm steps – 36 nm is the period of the helical actin filament
Sliding Filament Model
What is the duty cycle?
proportion of time during each cross-bridge cycle the myosin is attached to actin
- time spent in cross-bridge divided by time for full cross-bridge cycle
Sliding Filament Model
What is the duty cycle for non-muscle myosin?
0.5
- each myosin has 2 heads
- duty cycle of 0.5 means that each myosin head is bound to actin for half of the cycle (one myosin is bound for half of the cycle, and the other myosin is bound for the other half of the cycle)
- at least one myosin head is bound at all times, which will help prevent myosin from falling off the track of the microfilament
Sliding Filament Model
What is the duty cycle for muscle myosin?
0.05
- muscle myosin and non-muscle myosin have different functions
- myosin heads are sliding by actin filaments
- want cross-bridges to occur quickly, so that contraction can occur quickly, therefore myosin heads are being bound and detached quickly
Describe the two main ways to categorize muscle.
- striated (skeletal and cardiac) vs. unstriated (smooth)
- voluntary (skeletal) vs. involuntary (cardiac and smooth)
What are striated muscles composed of?
- thick filaments (myosin)
- thin filaments (actin)
What are thick filaments?
polymers of ~300 myosin II hexamers
What are thin filaments?
polymers of alpha-actin
(compare this to microfilaments, which are polymers of beta-actin)
What proteins are associated with thin filaments?
- special proteins that cap the ends of the filament to stabilize structure (filaments are fixed)
- structural proteins (ie. troponin, tropomyosin)
What filament is tropomyosin and troponin associated with?
thin filament
What does tropomyosin and troponin do?
regulate the interaction between actin and myosin in striated muscles
What is tropomyosin?
long, thin, double-stranded protein that extends over ~7 actin monomers on the thin filament
What is troponin?
trimer of (TnC, TnI, and TnT) that binds to every 7th actin on the thin filament
What role does the TnC of troponin play?
Ca2+ binds to it, which shifts tropomyosin and allows tropomyosin to interact with myosin
Sarcomere
What is the A-band?
the region where thick filaments occur
Sarcomere
What is the I-band?
the portion of the thin filaments that does not overlap with the thick filaments
- spans a Z-disk
Sarcomere
What is a Z-disk?
protein plate (composed of actin, titin, and other proteins) at the end of the sarcomere where the (+) end of actin thin filaments are attached
Sarcomere
What is the H-zone?
the portion of the thick filaments that does not overlap with the thin filaments
Sarcomere
What is the M-line?
the centre of the sarcomere between (-) ends of actin – region where thick filaments do not overlap with thin filaments
What is the sarcomere length-force relationship?
recall: cross-bridges can only form when the myosin heads of a thick filament can interact with the actin units of a thin filament
- the amount of force a sarcomere can produce during contraction increases as the number of myosin heads that can contact a thin filament increases
- the amount of force a sarcomere can produce decreases as overlap between the thin filaments of adjacent Z-disks increases
- at the shortest sarcomere length, the thick filaments will collide with the Z-disks and no further contraction is possible
Sarcomere Arrangements
What is a myofibril composed of?
many sarcomeres arranged in series
Sarcomere Arrangements
What is a myofibre (striated muscle cell) composed of?
many myofibrils arranged in parallel
Sarcomere Arrangements
What occurs when myofibres (striated muscle cells) grow in length?
it adds more sarcomeres to the ends of each myofibril
Sarcomere Arrangements
What occurs when myofibres (striated muscle cells) grow in diameter?
it increases the number of myofibrils
Sarcomere Arrangements
How long is a myofibril?
runs the entire length of a muscle cell
EC Coupling
Give an overview of the events in a typical skeletal muscle.
excitation leads to contraction:
- AP depolarizes sarcolemma (excitation)
- AP caused by opening of Ca2+ channels
- depolarization linked to Ca2+ release from SR
- Ca2+ channels in SR are linked to the Ca2+ channels that caused the AP (coupling)
- Ca2+ binds to troponin (TnC component specifically), which shifts the configuration of tropomyosin to reveal the myosin binding sites on actin
- cross-bridge cycling and sarcomere shortening (contraction
relaxation:
- sarcolemma repolarizes and cytoplasmic [Ca2+] returns to resting levels
EC Coupling – Excitation
Are most vertebrate skeletal muscles neurogenic or myogenic?
neurogenic (neuron causes excitation)
- they are stimulated by ACh from a motor neuron
EC Coupling – Excitation
Describe the innervation of cells in twitch muscles.
each cell is innervated by one neuron
EC Coupling – Excitation
Describe the innervation of cells in tonic muscles. Why does it differ from twitch muscles?
each cell is innervated by multiple neurons
- this is needed because tonic muscles always have some level of contraction
EC Coupling – Excitation
What is the sarcolemma resting membrane potential?
around -70 mV
EC Coupling – Excitation
What causes depolarization?
- opening of Na+ channels, allowing influx of Na+
- then opening of voltage-gated Ca2+ channels, allowing influx of Ca2+
EC Coupling – Excitation
What causes repolarization?
- opening of K+ channels, allowing K+ to leave the cell
- then opening of Cl- channels (in SKELETAL muscle)
EC Coupling – Excitation
Is the time course of an AP in a muscle cell always the same?
no – varies in different types of muscle
EC Coupling – Excitation
Neurogenic twitch muscles are innervated by one (or maybe a couple) motor neurons. How do muscles ensure uniform depolarization of the sarcolemma for contraction?
- multiple innervations (for tonic muscles)
- invaginations of the sarcolemma called t-tubules, which propagate the AP to multiple places
EC Coupling – Excitation
What are transverse or t-tubules? What do they do? Where are they found?
sarcolemmal invaginations that enhance AP penetration
- more developed in larger, fast-twitching muscles
EC Coupling – Excitation
What does the sarcoplasmic reticulum (SR) do?
stores Ca2+
EC Coupling – Excitation
What are terminal cisternae? What do they do?
enlargements in the SR that increase Ca2+ storage
EC Coupling – Coupling
Depolarization-induced Ca2+ release. How does this occur?
- depolarization of the sarcolemma causes DHPR to open
- DHPR and RyR are physically linked, and the structural change in DHPR opens RyR
- Ca2+ exits the SR through RyR, which greatly increases cytoplasmic [Ca2+] and stimulates contraction
- Ca2+ ATPase and NaCaX pump Ca2+ out of the cell, and SERCA pumps Ca2+ into the SR, which together decreases cytoplasmic [Ca2+] and allows relaxation
EC Coupling – Coupling
What does troponin and tropomyosin do during relaxation of the muscle?
- during relaxation, cytoplasmic [Ca2+] is low
- TnC (troponin) regulatory sites cannot bind Ca2+
- the troponin-tropomyosin complex blocks the myosin bindings sites on the thin filament
EC Coupling – Coupling
What does troponin and tropomyosin do during excitation of the muscle?
- excitation of the muscle increases cytoplasmic [Ca2+]
- TnC (troponin) regulatory sites bind Ca2+, which causes a structural reorganization of the troponin-tropomyosin complex
- the troponin-tropomyosin complex rolls into the groove of the thin filament, which exposes the myosin binding sites
What is a single twitch?
if a muscle fibre is restimulated after it has completely relaxed, the second twitch is the smae magnitude as the first twitch
What is twitch summation?
if a muscle fibre is restimulated before it has completely relaxed, the second twitch is added on to the first twitch
What is tetanus?
if a muscle fibre is stimulated so rapidly that it does not have an opportunity to relax at all between stimuli, a maximal sustained contraction known as tetanus occurs
- eventually, stimulation ceases or fatigue begins
Cardiac Muscle
How are cardiomyocytes arranged?
formed into a branching network
- cells are connected end-to-end by intercalated disks, which contain gap junctions through which APs are propagated to adjacent cells (myogenic)
Describe the difference in the arrangement of contractile units in skeletal vs. cardiac muscle.
- skeletal: linear along the long-axis of the muscle
- cardiac: branching network
Describe the difference in the type of innervation in skeletal vs. cardiac muscle.
- skeletal: somatic
- cardiac: autonomic
Describe the difference in the type of excitation in skeletal vs. cardiac muscle.
- skeletal: neurogenic – neural input needed for contraction
- cardiac: myogenic – cardiomyocytes contract in response to input from other muscle cells
Describe the difference in EC-coupling in skeletal vs. cardiac muscle.
- skeletal: depolarization-induced Ca2+ release
- cardiac: Ca2+-induced Ca2+ release
Cardiac Muscle
What are pacemaker cells? Where are they located?
specialized myocytes that depolarize spontaneously
- located in specific nodes
Cardiac Muscle
Do pacemaker cells have a stable or unstable membrane potential? Why?
unstable RMP, in part due to f-channels which are permeable to both Na+ and K+
Cardiac Muscle
What is the main difference between skeletal muscle and cardiac muscle APs?
timing
- cardiac muscle APs have a plateau phase, caused by the slow influx of Ca2+
EC Coupling – Cardiac Muscle
Ca2+-induced Ca2+ release. How does it occur?
- depolarization of the sarcolemma causes DHPR to open, which allows extracellular Ca2+ to enter the cell
- localized increases in intracellular [Ca2+] triggers the opening of RyR, which greatly increases cytoplasmic [Ca2+] and stimulates contraction
- Ca2+ ATPase and NaCaX pumps Ca2+ out of the cell, and SERCA pumps Ca2+ into the SR, which together decreases cytoplasmic [Ca2+] and allows relaxation
EC Coupling
Describe the difference in coupling in skeletal vs. cardiac muscle.
- in skeletal muscle, dihydropyridine receptors (DHPR) and ryanodine receptors (RyR) are physically linked, which allows for depolarization-induced Ca2+ release from the SR
- in bird and mammal cardiac muscle cells, DHPR and RyR are NOT physically linked
What happens when cardiac muscle is stimulated at a higher frequency? How does this compare to skeletal muscle?
- a point is reached where stimulation occurs while the AP is in the refractory period
- contractions may or may not occur, and the normal frequency is lost (arrhythmia)
- in skeletal muscle, twitch summation or tetanus occurs
What shape does smooth muscle have?
spindle-shaped
- no set structure like sarcomeres
- thick filaments (myosin) and thin filaments (actin) go all around the cell
What aspects of smooth muscle cell shape are affected when contraction occurs? How does this compare with skeletal muscle?
- contraction affects depth, width, and length of the cells
- in skeletal muscle, only length changes
Why do smooth muscle contract slower than skeletal muscle?
they have a longer duty cycle
Smooth Muscle
Regulation of Contraction – Thick Filament
- Ca2+ enters the cell and is also released from SR, which increases intracellular [Ca2+]
- Ca2+ binds to calmodulin
- Ca2+-CM activates myosin light chain kinase
- activated MLCK phosphorylates the light chains in myosin heads, which increases myosin ATPase activity
- active myosin cross-bridges slide along actin, which results in muscle tension
Smooth Muscle
What does myosin light chain phosphatase (MLCP) do?
removes phosphorous from myosin head
Smooth Muscle
Does smooth muscle have troponin and tropomyosin?
lacks troponin
- instead, the position of tropomyosin on the actin filament is regulated by caldesmon