Flashcards in Skeletal Muscle Review Deck (57):
Why does the alpha-motorneuron act as the final common pathway for motor unit activation?
It integrates excitatory and inhibitory inputs
Botulinum toxin (Botox) prevents release of Ach from the motoneuron, resulting in what?
decreases the magnitude of the graded depolarization in the neuromuscular junction
Skeletal muscle is innervated by motorneurons from where?
ventral horn of the spinal cord. The axon of these motorneurons diverges in the skeletal muscle bed to innervate multiple muscle fibers.
T or F. Each muscle fiber receives innervation from only one motorneuron.
What is the main role of the motoneuron body?
It acts as an integrator of excitatory and inhibitory synapses
impinging upon its cell membrane, and thus acts as a Final Common Pathway for muscle fiber contraction.
The motorneuron and the muscle fibers that it innervates are called a
motor unit. When the motorneuron generates an action potential, all fibers within the motor unit will contract.
What are the types of motoneuron cell bodies?
large and small
Describe small motoneuron cell bodies.
In general, these motorneurons will innervate relatively few muscle fibers. These
muscle fibers also have a tendency to have relatively small cross-sectional diameters.
Such motor units are routinely referred to as slow motor units because of their
In contrast, large motoneuron bodies innervate many and are called fast motor units
What happens when an action potential reaches the nerve terminal?
Ach is released from
synaptic vesicles into the synaptic cleft through normal, Ca2+-mediated synaptic
What is the target for the released acetylcholine?
Nicotinic M acetylcholine
receptors in the motor end-plate on the muscle.
Describe nicotinic Ach receptors.
monovalent cation channels (for Na+ AND K+), so activation of these channels will generate a graded depolarization.
The motor end-plate is very dense with nicotinic acetylcholine
receptors and has very few voltage-gated sodium channels.
What must occur for activation of the voltage-gated sodium channels that reside
in the surrounding membrane around the nicotinic receptors?
a sufficient number of receptors must be activated in order to bring the surrounding membrane above
threshold for an action potential
What happens once an action potential is reached?
an action potential is initiated that propagates along the muscle fiber membrane as it would in an unmyelinated nerve axon
What conducts the membrane depolarization along the muscle fibers toward the SR?
What does depolarization of the T-tubule membrane cause?
The depolarization of the T-tubule membrane has the effect of causing a conformation
change in the dihydropyridine receptor
What does the change in conformation of the dihydropyridine receptor do?
In skeletal muscle, this activates a calcium channel in the SR, the ryanodine receptor
What does opening of the ryanodine receptor cause?
Opening of this calcium channel allow the passive efflux of calcium from the SR store, rapidly elevating intracellular Ca2+ concentration.
The unit from one Z-line to the next is called what?
What are thick filaments proteins?
myosin heavy chains, large proteins with a filamentous tail and a globular head, along with two light chains per head
How are myosin heavy chains typically composed?
Myosin heavy chains tend to form dimers, and these dimers form the bipolar thick filament with globular heads
directed outward and the heavy chains on one end of the filament aligned in the opposite
direction from those at the other end of the filament.
What is the major protein of thin filaments?
actin (and tropomyosins and troponins)
What shape do actin filaments take on?
helical chains under the correct conditions
monomer has a high-affinity binding site for the myosin heads.
What is the role of tropomyosins?
These are fibrous proteins that extend along the length of the thin filament such that tropomyosin can cover the myosin binding sites on the actin
What is the structure of troponin molecules?
They form a ternary complex of troponin C, a calcium binding protein, troponin T, a tropomyosin binding protein, and troponin I, a protein that keeps the troponin complex in a position such that tropomyosin covers the myosin binding site on the actin molecules when calcium is not present in sufficiently high concentrations.
How is tropomyosin arranged when Ca2+ levels are low?
such that there cannot be myosin-actin interaction.
What happens when Ca2+ is released from the SR?
calcium binds to troponin C, causing a conformation change that moves the tropomyosin deeper into the helical cleft of the fibrous actin. This uncovers the binding site for myosin on actin,
allowing myosin to interact and produce force.
How is force produced from myosin interacting with actin?
the ATPase activity in the myosin head consumes energy to produce a mechanical force.
Specifically, how is forced generated?
When ATP has been hydrolyzed and the resulting ADP remains bound to the myosin head, the myosin head goes into a high affinity state for binding actin.
What is the 'hinge'?
Once bound to actin, a conformation change takes place near where the globular head and fibrous tail of the myosin heavy chain connect, the so-called hinge
What is the result of the conformation change resulting in the hinge?
The conformation change has the effect of attempting to pull the thick filament toward the Z-line. Because the thick filament is bipolar, the net effect is to draw the Z-lines toward one another. This is called the power stroke.
T or F. Myosin and actin will remain bound to one another as long as ADP is bound to the myosin head
What happens to myosin affinity for ADP once the power stroke occurs?
the myosin head has a much higher affinity for ATP, so ATP displaces ADP, lowering the myosin-actin affinity and allowing the myosin head to release.
ATP is then hydrolyzed and the cross-bridge cycling begins again. In response to a single action potential, only a few cross-bridge cycles occur.
What causes rigor mortis?
The inability to actively pump calcium back into the SR along with the inability to release the myosin-actin cross-bridge (both due to lack of ATP)
What is peak tension?
Attaching a muscle, or muscle fiber, to an apparatus in which we can adjust the length reveals that muscle exerts a passive tension in the absence of any contractile activity. This is much like a rubber band, with intracellular and extracellular proteins providing an elastic force that opposes an increase in length. If the muscle is adjusted to a set length and an action potential is initiated, the peak tension measured will be the sum of the passive tension and the active tension due to myosin-actin interaction.
T or F. The active tension has a maximum at a
specific, optimal length.
What occurs at the optimal sacromere length?
every myosin head can contribute force. Also note that the passive tension of the muscle or its fibers reaches nearly zero at the
optimum length (where active tension is highest).
What is a twitch?
the isometric mechanics of the
muscle to a single action potential
What is the half-relaxation time?
the time required to relax to one-half the peak isometric tension using a tension transducer
How would ryanodine poisoning present?
During routine physical exam of a new patient you note normal muscle reflex contraction but slow muscle reflex relaxation. You ask whether the patient has hypothyroidism. Why?
Slows calcium uptake by the SR via gene changes in ATPase expression
T or F. For any given force, fast motor units will develop
greater velocity of shortening.
T. Likewise, for any given velocity of shortening, fast motor units will develop greater force.
Why is the maximal velocity of shortening more in fast units?
Due to the expression of myosin with more rapid kinetics of cross-bridge cycling
Which sized motor neurons are recruited faster for action?
Because of the smaller surface area of a smaller motorneuron body, on average these motorneurons require fewer active excitatory synapses in order for a threshold depolarization to occur in the axon hillock.
What is tetanic tension?
the tension produced by the slow motor unit eventually reaches a maximum. Also note that this tetanic tension is greater than the twitch tension.
T or F. Slow motor units produce a tetanic contraction at a frequency of activation that is less than for fast motor units.
T. It is also clear that slow motor units produce less tetanic force than fast motor units.
Velocity of shortening is directly related to what?
myosin ATPase activity (greater in fast motor neurons)
How is ATP regenerated from ADP on myosin heads?
creatine-P is converted to creatine by creatine kinase
High creatinine with normal CK and LDH suggests what?
kidney disease decreased clearance
High creatinine with elevated CK and LDH suggests what?
muscle disease causing overproduction
Describe metabolism of slow motor units.
The muscle fibers have a high mitochondrial density and
are rich in myoglobin, producing ATP by oxidative phosphorylation.
Are slow motor units susceptible to fatigue?
Because the myosin expressed in these muscle fibers consumes ATP at a relatively slow rate, these fibers are unlikely to be impaired in their ability to produce sufficient energy to produce sustained
These slow, oxidative motor units are found in postural muscle.
Describe metabolism of fast motor units.
These have muscle fibers whose metabolism is almost entirely glycogenolytic. Because the myosin expressed in these muscle fibers consumes ATP rapidly, and the storage of glycogen is limited, these fast, glycogenolytic fibers rapidly reach a point where contraction cannot be sustained (fatigue).
T or F. Motor units, and the fibers within the motor units, are very plastic with respect to their gene expression in response to use and disuse.
T. Adaptations in gene expression tend to
favor economy of energy expenditure to perform tasks.
How do motor units adapt to resistance tasks (high energy use)?
increases muscle fiber diameter, shifts toward more fast myosin expression, and increases glycogenolytic metabolism
How do motor units adapt to endurance tasks (low energy use)?
favor changes in gene
expression that shift toward slow myosin expression and more oxidative metabolism and muscle fiber size doesnt change much
T or F. Our postural muscles, which are used imperceptibly all day, every day for
what is really an endurance task, will rapidly adapt to a condition of disuse.