Muscles Flashcards
What does the “I” in I band stand for? What does it contain?
Isotropic- it appeared white under polarized microscopy. Thin (actin) filaments
What does the “A” in A band stand for? What does it contain?
Anisotropic- it appeared dark under polarized microscopy. Thick (myosin) filaments
Order these from largest to smallest: sarcomere, myofiber, myofibril, fascicle, myofilament
fascicle-> myofiber -> myofibril-> myofilament-> sarcomere
What does the Z line denote?
The boundary between two sarcomeres
What is special about the H zone?
It is where there is no overlap between thick and thin filaments
What does the M line denote?
It is the site a which thick filaments are linked with each other
What happens during the sliding filament model of muscle contraction? What changes are visible under the microscope?
Thick and thin filaments slide past each other. Sarcomeres shorten- the Z-lines move closer together and the I band shortens
What part of myosin does work?
The two heavy chains. They hydrolyze ATP and bind actin
What part of myosin is regulatory?
Two of the light chains. They are phosphorylated by a Ca2+- dependent kinase
What needs to happen before skeletal muscle contraction can begin in a sarcomere?
A motor neuron must bring an action potential to a myofibril and release acetylcholine. Na+ must enter the muscle and cause the release of Ca2+ from the sarcoplasmic reticulum. Ca2+ must bind to troponin C which moves tropomyosin off of the myosin-biding sites on the actin filaments
What are the three subunits of troponin? What do they each do?
Troponin C- binds Ca2+
T- binds to tropomyosin
I- binds to actin. (Inhibits actin-myosin binding)
What are the steps in the cross-bridge cycle for skeletal muscle?
- ATP binds to the myosin head. It detaches from actin
- Myosin head hydrolyzes ATP. It is cocked
- Myosin forms a cross bridge with a new site on actin
- Myosin releases Pi, “snaps shut”, filaments slide past each other (power stroke)
- Myosin releases DP and stays bound to actin
How does Ca2+ regulate muscle contraction in muscle?
Through the binding of troponin and tropomyosin and through phosphorylation of myosin
Define: twitch
The contraction generated by a single action potential. Measured in tension
How do fast and slow twitch muscle types differ?
They contain different types of myosin and different amounts of mitochondria and myoglobin. Fast does more glycolysis; slow does more oxidative metabolism.
What is the relationship between muscle length and tension? Why is it this way?
At at optimal length, the muscle has the greatest overlap between thick and thin filaments and produces the greatest force/tension. Tension increases with increasing length til that point and decreases with increased length past it.
What are satellite cells? What do they do?
Cells that allow for normal muscle repair and hypertrophy due to exercise. They fuse with muscle fibers to increase the number of nuclei, amount of cytoplasm and proteins produced and connective tissue.
What is myostatin? What is its relationship to exercise?
It controls muscle fiber growth. Exercise decreases it in muscles.
What are t-tubules?
Transverse tubules. Invaginations of the sarcolemma that convey the action potential from the surface to individual muscle fibers
How does a neuron convey an action potential to a muscle fiber?
The action potential leaps down the neuron between nodes of ranvier (saltatory conduction). It depolarizes the bouton, opening voltage-gated Ca2+ channels. The calcium influx triggers Ach vesicles to fuse with the membrane. Ach binds to nicotinic receptors on the muscle fiber, depolarizing the membrane and opening voltage-gated Na+ channels, causing an action potential in the muscle fiber.
Where could a toxin block neuromuscular activity in the synapse?
At Ca2+ channels on the neuron; at Na+ channels and nicotinic receptors on the muscle fiber; also could disrupt vesicle fusion in the neuron
What is myasthenia gravis? Where does it affect the process of excitation contraction coupling?
An autoimmune disease in which the body targets Ach receptors. Often affects the eyes and mouth.
At the neuromuscular junction
Where does Gullian-Barre affect the process of excitation contraction coupling? Generally, what is it?
In the neuron. It is an autoimmune disease that targets myelin in the peripheral NS
Where does ALS (amyotrophic lateral sclerosis) affect the process of excitation contraction coupling? Generally, what is it?
At the motor neuron. It causes death of motor neurons
Where does muscular dystrophy affect the process of excitation contraction coupling? Generally, what is it?
At the muscle. It is a weakening of the connection between the myofiber and the ensheathing ECM so that contractions tear the muscle apart.
Where does malignant hyperthermia affect the process of excitation contraction coupling? Generally, what is it?
In the sarcomeres. It is a mutation in the ryanodine receptor, causing excessive Ca2+ release into the muscle
Describe how calcium is typically released in skeletal muscle
A muscle action potential (Na+ driven) depolarizes the sarcolemma. This opens voltage-sensitive L-type Ca2+ channels (DHP receptors) in the membrane which are physically coupled with ryanodine receptors in the SR, thus releasing Ca2+ in the SR.
How does skeletal muscle relax?
When Ca2+ is removed from the sarcoplasm. This happens mostly by a Ca2+ ATPase in the SR (SERCA) but also by a Ca2+ ATPase in the sarcolemma (PMCA) and by a Na+/Ca2+ exchanger (NCX) in the membrane
What is the skeletal muscle triad? Why is it significant?
A t-tubule adjacent to 2 terminal cisternae of SR. It allows for physical coupling of the L-type Ca2+ membrane channels (DHP receptors) with the ryanodine receptors in the SR
What are calsequestrin and calreticulin?
They are proteins in the SR that bind Ca2+
How is a muscle twitch related to Ca2+ levels in the sarcoplasm?
Tension development in a twitch parallels Ca2+ release in a cell (with a delay). Additionally, twitch duration directly parallels Ca2+ duration in a specific type of muscle (i.e. fast or slow twitch)
What is temporal summation?
When a motor neuron fires action potentials to a muscle before the muscle can completely clear the Ca2+ from it’s sarcoplasm and contractions increase in tension.
What is muscle tetanus? What is the difference between fused and unfused?
A very high frequency of motor neuron action potentials causes muscle tension to summate. In unfused tetanus, tension oscillates as some Ca2+ is cleared from the sarcoplasm.
What is treppe?
Increasing muscle tension with increasing stimuli. It is NOT summation
Define: motor unit. How big is it for fast twitch muscle? Slow twitch muscle?
One motor neuron and all myofibers it innervates. An action potential causes the whole motor unit to contract simultaneously. Fast twich muscles have large motor units; slow twitch muscles have smaller ones.
What is motor neuron recruitment?
Small motor units fire first. If they cannot create the tension needed for a contraction, larger units are recruited to contract in addition to the small units to generate the tension needed.
What are the two mechanisms by which skeletal muscle regulates force? Which is more important?
Action potential summation and motor unit recruitment. Motor unit recruitment.
What energy sources are available to fast-twitch muscle? About how long does this provide energy?
ATP, Phosphocreatine and anaerobic (glycolytic) metabolism. 60 seconds.
What energy sources are available to slow-twitch muscle? About how long does this provide energy?
ATP, Phosphocreatine, and both anaerobic and aerobic metabolism. 4 hours
What does phosphocreatine do?
It rapidly transfers Pi to ADP, regenerating ATP. It only works for 5-8 seconds in a muscle though.
What are some probable causes of muscle fatigue?
Depletion of SR Ca2+, buildup of Pi and/or lactic acid (increased pH-> troponin C and myosin are less efficient). NOT ATP depletion
How does smooth muscle organization differ from that of skeletal muscle?
It does not have sarcomeres, striations, A bands or I bands. It does have thick and thin filaments and is anchored to dense bodies.
Describe smooth muscle contractions in relation to those of skeletal muscle.
They are slower in velocity and relaxation. Smooth muscle can contract to a much smaller length than skeletal muscle though and has a very high maximal force of contraction.
Define: calveoli. What is their significance?
Domains of the sarcolemma with lots of receptors and ion channels. They are in close proximity to the SR and mitochondria and are the site of a lot of cell signaling
What ion is the smooth muscle action potential dependent on?
Ca2+ (skeletal is Na+-dependent). It is not dependent on membrane depolarization.
How is smooth muscle organized? Where are these types of organizations found in the body?
As unitary (1 neuron innervates many cells, AP spreads through gap junctions) and multiunit (each muscle cell is innervated by 1 neuron) muscle. Unitary- GI tract. Multiunit- piloerector muscles.
Does unitary muscle respond to stretch? Sympathetic activation? What about multi-unit?
Unitary- stretch. Multi-unit- sympathetics
How does Ca2+ enter the sarcolemma of a smooth muscle cell?
- Electromechanically- an action potential or stretch opens voltage-gated L-type Car2+ channels in the calveoli, binds to channels on the SR to stimulate more Ca2+ release.
2- Pharmacomechanically. A ligand binds a GPCR which activates phospholipase C which makes IP3 which binds a receptor on the SR to release Ca2+
What is myosin light chain kinase? What does it do?
It is the key regulatory protein in smooth muscle. Is is active in the presence of Ca2+ and calmodulin. It phosphorylates the regulatory light chain on myosin to activate it so smooth muscle can contract
What is myosin light chain phosphatase? What does it do?
It dephosphorylates the myosin regulatory light chain, inactivating myosin and allowing smooth muscle to relax.
What is basal electrical rhythm? What is its significance?
Rhythmic subthreshold depolarizations of smooth muscle. When the muscle is innervated, the stimulus superimposes on the BER so that contractions can occur at a certain rhythm (i.e. peristalsis)
How does the smooth muscle crossbridge cycle differ from that of skeletal muscle?
- There is no tropomyosin/troponin involved. MLCK instead
- Latch bridge state- during rigor, MLCP can cleave Pi from myosin. Myosin can’t bind ATP and thus maintains tension without using ATP often at low Ca2+ levels
What is endothelin? How does it work?
It is a peptide released by endothelial cells that stimulates initial smooth muscle relaxation followed by contraction. It binds ET-B receptors on endothelial cells, stimulating production of NO which increases smooth muscle cGMP and causes relaxation. It also binds ET-A receptors on smooth muscle, causing IP3 production, increased cytosolic Ca2+ and contraction.
How does smooth muscle respond to epinephrine? Where do these responses take place?
Skin and gut arteriolar smooth muscle- epi binds alpha1 receptors, causing IP3 production, SR Ca2+ releases and contraction (vasoconstriction).
Heart and skeletal muscle arteriolar smooth muscle and bronchiolar smooth muscle- epi binds B2 activating adenylyl cyclase, making cAMP and activating protein kinase A which inhibits MLCK so MLCP can relax smooth muscle causing dilation.
What is active hyperemia? What might cause it?
Increased blood flow through a tissue b/c of increased activity. May be because low O2 causes arteriolar sphincters to relax and/or because of release of vasodilatory substances (adenosine).
How does adenosine relax smooth muscle?
- Binds A2 adenosine receptors which stimulate adenylyl cyclase, increase cAMP, stimulate protein kinase A and downregulate MLCK (thereby upregulating MLCP)
- A1 adenosine receptors open K+ channels in the membrane, repolarizing/hyperpolarizing the muscle.
What is stress relaxation of smooth muscle?
When a vessel is stretched, it’s pressure does not remain constant but instead decreases over time probably due to elastin content in the smooth muscle.
How does the stomach stretch? (hint: NO, VIP involved)
Stretch receptors stimulate the vagus which releases Ach and VIP (vasoactive intestinal polypeptide) and also makes NO. Ach binds M3 receptors which increase NO production in endothelial cells. VIP decreases smooth muscle Ca2+ concentrations and NO increases cGMP both of which cause relaxation and distention of the stomach.
Do isometric contractions do work? Do they have power?
No change in length so no work and thus no power.
How is there no movement of load in an isometric twitch?
Contractile elements (muscle) contract but series elastic elements (tendons) stretch for no net change in length
Do isotonic contractions do work? Do they have power?
Yes and yes. There is a change in length.
What are the 4 phases of an isotonic twitch?
Isometric contraction (builds tension to lift the object), isotonic contraction (lifts object), isotonic relaxation (setting object down), isometric relaxation (once the object has touched down)
As load increases, what happens to isotonic twitch velocity of shortening? Amount of shortening? Duration of shortening? Length of latent period? Force necessary to lift the load?
Velocity, amount and duration decrease.
Force and latent period increase.
At what load is velocity of contraction maximal?
Zero load
What type of contraction occurs when the load is equal to or greater than the maximum tension of the muscle?
Isometric b/c no shortening will occur
Define: preload, afterload and total load. How are they related?
Preload- the weight that pulls the muscle to the initial length to develop tension
Afterload- equivalent to the total tension. The load you want to lift
Total load= preload + afterload. Total load lifted
When are isotonic contractions used? Isometric contractions?
Isotonic- to move things
Isometric- to maintain posture
