Cellular Physiology (Part 3) Flashcards
What are the 3 characteristics of a muscle fiber?
- it functions as a single unit
- multinucleated
- contains myofibrils
Myofibrils of a muscle fiber are surround by _____ and are invaginated by _______.
endoplasmic reticulum
transverse tubules (T tubules)
What are the thick filaments composed of in a myofibril?
myosin
Describe the structure of myosin
It is comprised of 6 polypeptide chains (2 heavy and 4 light chains). The heavy chains coil around one another to form the “tail” of the myosin molecule. The 4 light chains and the N terminus of each heavy chain forms 2 globular “heads” which contain an actin-binding site, which is necessary for cross-bridge formation
What are the thin filaments composed of in a myofibril?
- actin
- tropomyosin
- troponin
What is the difference between G-actin and F-actin?
When actin is in its globular protein form it is called G-actin.
When actin is twisted into an alpha-helix structure to form filamentous actin it is called F-actin
Which form of actin is present in thin filaments?
F-actin
Describe the shape actin is in when the muscle is at rest?
The myosin-binding sites on the actin are covered by tropomyosin and troponin so that actin and myosin cannot interact
What is tropomyosin’s function?
It blocks myosin-binding sites on actin during rest, and when muscle contraction occurs it is moved out of the way so the 2 can interact
What are the 3 globular proteins that form troponin?
- troponin T
- troponin I
- troponin C
What is the function of troponin T?
It attaches the troponin complex to tropomyosin
What is the function of troponin I?
It inhibits the interaction of actin and myosin by covering the myosin-binding sites (with tropomyosin)
What is the function of troponin C?
It is a Ca2+ binding protein that plays a central role in the initiation of contraction
What happens at troponin C when Ca2+ concentration is high?
Ca2+ binds to troponin C, producing a conformational change in the troponin complex which moves tropomyosin out of the way, permitting the binding of actin to the myosin heads
What is the basic contractile unit of skeletal muscle?
sarcomere
Describe the structure of a sarcomere
Each sarcomere contains a full A band and one half of 2 I bands on either side of the A band
What structure denotes one sarcomere from the next?
Z disks
What are A bands?
They are bands located in the middle of the sarcomere that contain the thick (myosin) filaments and also an overlap of thick and thin (actin) filaments which are potential sites of cross-bridge formation
What are I bands?
They are bands located on either side of the A band that contain thin (actin) filaments, intermediate filamentous proteins, and Z discs.
*contain no thick filaments
What is the bare zone of a sarcomere?
The center of each sarcomere in which there is no thin filaments, thus there can be no overlap of thick and thin filaments or cross-bridge formation
What is the M line?
The line in the sarcomere that bisects the bare zone and contains darkly staining proteins that link the central portions of the thick filaments together
What proteins establish the architecture of the myofibrils, ensuring that the thick and thin filaments are aligned correctly and at proper distances with respect to each other
cytoskeletal proteins
What do transverse cytoskeletal proteins do?
They link thick and thin filaments, forming a “scaffold” for the myofibrils and linking sarcomeres of adjacent myofibrils
What actin-binding protein anchors the entire myofibril arrangement to the cell membrane?
dystophin
Patients with a defective or absent dystrophin protein have what pathology?
muscular dystophy
Longitudinal cytoskeletal proteins include what 2 proteins?
titin and nebulin
Describe the structure of titin
It is a large molecular weight protein that extends from the M lines to the Z discs through the thick filaments
Describe the structure of nebulin
This molecule extends from one end of the thin filament to the other serving as a “molecular ruler”, setting the length of the thin filaments during their assembly
What anchors the thin filaments to the Z disc?
alpha-Actinin
What is the function of the T tubules?
They are responsible for carrying depolarization from action potentials at the muscle cell surface to the interior of the fiber
The sarcoplasmic reticulum is the site or what?
storage and release of Ca2+ for excitation-contraction coupling
What part of the endoplasmic reticulum comes into contact with the T tubules?
the terminal cisternae
Describe the action of Ca2+ ATPase in the sarcoplasmic reticulum
It pumps Ca2+ from the ICF of the muscle fiber into the interior of the sarcoplasmic reticulum which keeps the intracellular Ca2+ concentration low when the muscle fiber is at rest
What binding-protein binds to Ca2+ in the sarcoplasmic reticulum to help keep the concentration of free Ca2+ ions inside the sarcoplasmic reticulum low?
Calsequestrian
What is the significance of keeping the concentration of Ca2+ concentration low in the sarcoplasmic reticulum?
It reduces the work of the Ca2+ ATPase pump
What is excitation-contraction coupling?
The mechanism that translates the muscle action potential into the production of tension
Describe the 3 temporal sequence of events in excitation-contraction coupling in skeletal muscle
1) muscle action potential
2) rise in intracellular Ca2+ concentration
3) muscle contraction
What are the 7 steps involved in excitation-contraction coupling?
1) action potentials in the muscle cell membrane are propagated to the T tubules by the spread of local currents
2) depolarization of the T tubules causes a critical conformational change in its voltage-sensitive dihydropyridine receptor which opens the Ca2+ release channels on the sarcoplasmic reticulum
3) Ca2+ is released from its storage site in the SR into the ICF of the muscle fiber, resulting in an increase in intracellular Ca2+ concentration
4) Ca2+ binds to troponin C on the thin filaments, causing a conformational change in the troponin complex
5) the conformational change in troponin causes tropomyosin to be moved out of the way so that cross-bridging cycling can begin
6) myosin heads bind to actin and form cross-bridges
7) Relaxation occurs when Ca2+ is reaccumulated in the SR by the Ca2+ ATPase
Describe the sequence of events in the cross-bridge cycle
1) No ATP is bound to myosin, and myosin is tightly attached to actin in a “rigor” position
2) ATP binds to the cleft on the back of the myosin head which produces a conformational change in myosin that decreases its affinity for actin, thus myosin is released from the original actin-binding site
3) The cleft closes around the bound ATP molecule, producing a further conformational change in myosin that causes myosin to be displaced toward the plus end of actin and ATP is hydrolyzed to ADP and Pi
4) Myosin binds to a new site on actin (toward the plus end) constituting the power stroke
5) ADP is released and myosin is returned to its original state with no nucleotides bound (rigor state)
How far does the myosin head “walk” along the actin filament during each power stroke?
10 nm
What happens if there is insufficient time for the SR to reaccumulate the Ca2+ and the intracellular Ca2+ concentration never returns to the low levels that exist during relaxation?
There is continued binding of Ca2+ to troponin C and continued cross-bridge cycling. In this state there is a sustained contraction called tetanus, rather than a single twitch
The _____-_____ relationship in muscle refers to the effect of muscle fiber length on the amount of tension the fiber can develop
Length-Tension Relationship
What are the 3 measurements of tension?
- passive
- total
- active
What is passive tension?
The tension developed by simply stretching a muscle to different lengths
What is total tension?
The tension developed when a muscle is stimulated to contract at different preloads
Total tension is the sum of what 2 things?
The active tension developed by the cross-bridge cycling in the sarcomere and the passive tension caused by stretching the muscle
How does active tension represent?
The active force developed by cross-bridge cycling
How can you determine active tension?
Subtract passive tension from the total tension
Active tension is ________ to the number of cross-bridges. What does this mean?
proportional
When there is maximal active tension, there is maximal overlap of thick and thin filaments and maximal possible cross-bridges
The _____-_____ relationship demonstrates the relationship between the velocity of shortening when the force against which the muscle contracts (afterload) is varied
force-velocity
In a force-velocity relation what is fixed?
The force, thereby producing an isotonic contraction
During a isotonic contraction what does the velocity of shortening reflect?
The speed of cross-bridge cycling
The velocity of shortening will be maximal when the afterload on the muscle is ____.
zero
What distinguishes smooth muscle from skeletal and cardiac muscle?
it lacks striations due to the unorganized nature of the sarcomeres
What are the 2 functions of smooth muscle?
- To produce motility
- To maintain tension
What are the 2 types of smooth muscle?
- Unitary
- Multiunit
What type of smooth muscle has gap junctions between cells, which allows for the fast spread of electrical activity throughout the organ, followed by a coordinated contraction?
unitary
Where can unitary smooth muscle be found?
In the GI tract, bladder, uterus, and ureter
What determines the frequency of contractions in unitary smooth muscle?
Spontaneous pacemaker activity called slow waves
What type of smooth muscle has little or no coupling between cells?
multiunit
Where can multiunit smooth muscle be found?
in the iris, ciliary muscles of the lens, and in the vas deferens
What innervates multiunit smooth muscle?
Postganglionic fibers of the parasympathetic and sympathetic nervous systems
What are the 3 mechanisms that increase intracellular Ca2+ concentration in smooth muscle?
- voltage-gated Ca2+ channels
- ligand-gated Ca2+ channels
- IP3-gated sarcoplasmic reticulum Ca2+ channels
