Lecture 4: Skeletal Muscles

Question 1

synaptic connection between a motor nerve and a skeletal muscle.

Answer 1

neuromuscular junction

Question 2

Nerves that regulate skeletal muscle function are called

Answer 2

motor nerves

Question 3

When an action potential arrives at the nerve (axon) terminal, it causes the release of the neurotransmitter _____

Stored in membrane-bound secretory vesicles which, upon the arrival of the action
potential at the axon terminal, fuse with the plasma membrane and release _____ into the synaptic
cleft between the pre-synaptic cell (the neuron), and the post-synaptic cell (the muscle fibre).

Acetylcholine then binds to an acetylcholine receptor on the post-synaptic membrane (i.e., the muscle cell membrane; called the sarcolemma).

In this case, the Ach receptor is a nicotinic acetylcholine receptor (or simply a nicotinic receptor) because it is also activated by nicotine. The nicotinic receptor is a Na+
channel and the binding of Ach to the receptor opens the channel and Na+
enters the muscle
cell, depolarises it and triggers an action potential in the muscle cell.

Answer 3

acetylcholine (Ach).

Question 4

Skeletal muscle cells are called

They are very long, multi-nucleated cells that are
packaged, with connective tissue, into bundles called fascicles. In turn, the whole muscle consists of multiple fascicles surrounded by layers of connective tissue. The muscle fibre consists of myofibrils which are bundles of actin and myosin filaments. As described below, contraction of skeletal muscle involves the actin and myosin fibres sliding over one another.

They are very long, multi-nucleated cells that are
packaged, with connective tissue, into bundles called fascicles. In turn, the whole muscle consists of multiple fascicles surrounded by layers of connective tissue. The muscle fibre consists of myofibrils which are bundles of actin and myosin filaments. As described below, contraction of skeletal muscle involves the actin and myosin fibres sliding over one another.

Answer 4

muscle fibres.

Question 5

If you look at the myofibrils in cross section using an electron microscope, you see large round dark
structures surrounded by six smaller round dark structures. The larger structures are the myosin
molecules (the thick filaments) and the smaller structures are the actin molecules (the thin filaments). If
you look at the myofibrils from a longitudinal perspective, you see a repeating arrangement of the thick
and thin filaments. Each of these repeating units is called a ______. When a muscle contracts the
thick (myosin) and thin (actin) filaments slide past each other causing the muscle to shorten. This
sliding takes place within each individual sarcomere. In other words, filaments in one sarcomere slide
over each other but not over filaments in other sarcomeres.

Answer 5

sarcomere

Question 6

The ______ is made up of two strands of actin molecules that form a double helix.

Each individual actin molecule within both strands has a binding site for myosin (the component of the
thick filament). When the thick and thin filaments are not sliding across one another, a long regulatory
protein called {tropomyosin} covers all of the myosin-binding sites on the actin molecules. In order for
the thick and thin filaments to slide across one another and cause muscle contraction, tropomyosin must
change configuration in order to expose these myosin-binding sites on actin.

Answer 6

thin filament

Question 7

______ is a second regulatory protein associated with the thin filament. It binds to actin,
tropomyosin and Ca2+. Ultimately (as will be described below), Ca2+ (released from the sarcoplasmic
reticulum in response to an action potential traveling down the T-tubules) will bind to troponin. This
will cause a change in tropomyosin causing it to move away from the myosin-binding sites. This will
allow actin and myosin to bind together and slide across one another (the mechanical event involved in
muscle contraction)

Answer 7

Troponin

Question 8

made up of myosin molecules. Each myosin molecule consists of two subunits
that are wound together.

Each subunit has a _____ (which is where the winding together occurs) and a
_____.

The myosin head has two binding sites; one for actin (the actin-binding site) and one for ATP
(the ATPase site). Note then that actin has a binding site for myosin and myosin has a binding site for
actin. The ATPase site on the myosin head is an enzymatic site. When ATP binds there, the ATP is
hydrolysed to ADP and an inorganic phosphate (Pi).

Answer 8

thick filament

tail and head

Individual myosin molecules (the two intertwined subunits) bind together at their tails to form a
structure with tails on the inside and heads on the outside (the middle diagram below). Hundreds of
these bound myosin molecules come together to form the thick filament.

Question 9

The myosin heads can exist in two states:

Answer 9

a “low energy” state or a “high energy” state.

Question 10

The high energy state of myosin heads exists….

The low energy state of myosin heads exists….

The energy in the high energy state is used to slide the filaments over one another. The diagram below illustrates that the myosin head can be in a low energy state at times when it is bound to actin and at times when it is not bound to actin.

Similarly, the high energy state can exist at times when myosin is not bound to actin and also at times when myosin is bound to actin. This is discussed in detail below.

Answer 10

exists prior to the sliding of the thick and thin filaments over one another.

once the thick and thin filaments have finished (“one round”) of sliding over one another

Question 11

In order for a muscle to contract, actin (the thin filament) and myosin (the thick filament) must bind to each other and then slide over (across; past) one another causing the _____ to shorten.

All of the these _____ do this more-or-less simultaneously thereby causing the entire myofibril and therefore the entire muscle fibre and muscle as a whole to shorten. To facilitate binding of the thick and thin filaments, actin has a myosin-binding site and myosin has an actin-binding site. When the two filaments bind together the site of interaction is called a _____.

Answer 11

sarcomere

crossbridge

Question 12

_____ is initiated in response to stimulation of the muscle by the motor nerve. The AP arriving in the axon terminal causes acetylcholine to be released into the synaptic cleft.

Acetylcholine binds to the nicotinic receptor on the muscle cell membrane (sarcolemma). This receptor is a Na+channel and the binding of Ach to it causes the Na+ channel to open. Na+ enters the cell and causes the sarcolemma to depolarise (the membrane potential becomes more positive). This triggers an action potential which travels along the sarcolemma and down into the T-tubules. Once in the T-tubules, the action potential triggers the release of Ca2+ from the sarcoplasmic reticulum.

Answer 12

Muscle contraction

Question 13

The Arrival of the Action Potential

Answer 13

Muscle contraction is initiated in response to stimulation of the muscle by the motor nerve. The AP arriving in the axon terminal causes acetylcholine to be released into the synaptic cleft.

Acetylcholine binds to the nicotinic receptor on the muscle cell membrane (sarcolemma). This receptor is a Na+channel and the binding of Ach to it causes the Na+ channel to open.

Na+ enters the cell and causes the
sarcolemma to depolarise (the membrane potential becomes more positive). This triggers an action
potential which travels along the sarcolemma and down into the T-tubules. Once in the T-tubules, the
action potential triggers the release of Ca2+ from the sarcoplasmic reticulum.

Question 14

Binding of Calcium to Troponin

Answer 14

The calcium that is released from the sarcoplasmic reticulum enters the cytosol of the muscle cell and
binds to troponin. When Ca2+ binds to troponin, this leads to a conformational change in tropomyosin
causing tropomyosin to move away from the myosin-binding sites on actin.

The myosin binding sites
on actin are now exposed and available to bind to the actin-binding sites on myosin.

Question 15

The Stages of Force Generation

Answer 15

The binding of Ca2+ to troponin and the removal of tropomyosin from the myosin-binding site on actin
means that actin is now available to bind to myosin and cause muscle contraction. So, the thin filament
is ready but what about the thick filament? The diagram below illustrates the cycle of events that occur
in order to allow the thick and thin filaments to slide across each other and cause the muscle to
contract. This is a cycle of events that will keep occurring again and again as long as Ca2+ is around to
keep tropomyosin off the myosin-binding sites on actin.

It is easiest to begin looking at this cycle at point A. At this stage, the thick and thin filaments have just
completed a cycle of sliding past one another. Actin and myosin are still bound to one another and the
myosin head is in the low energy configuration. In order for actin and myosin to separate from one
another ATP is required (B). The binding of ATP to the ATPase site on the myosin head (C) causes
actin and myosin to detach from one another (D). However, the myosin head is still in the low energy
configuration. The hydrolysis of ATP to ADP and Pi (E) causes the myosin head to move into the high
energy configuration (F). At this stage, the ADP and Pi molecules are bound to the ATPase site on the
myosin head. Myosin is now ready. As long as actin is still ready (i.e., calcium is still around), the actin
molecule forms a crossbridge with the myosin molecule with the myosin heads in the high energy
configuration (G). The binding of the actin and myosin molecules causes the inorganic phosphate (Pi)
to be released from the ATPase site (H). The removal of the inorganic phosphate causes the myosin
head to pivot from the high energy configuration to the low energy configuration (I) pushing the actin
filament toward the middle of the sarcomere in the power stroke (J). The movement of the actin
filament causes the ADP molecule to be released from the ATPase site (K). We are now back to the
beginning (A); actin and myosin are bound together and the myosin head is in the low-energy state.

Question 16

Terminating Contraction

Answer 16

As long as the motor neuron is firing action potentials and stimulating the muscle cell, action potentials
will be traveling down the T-tubules and causing calcium release from the sarcoplasmic reticulum. As
long as calcium is available to bind to troponin, tropomyosin will be kept off the myosin-binding sites
on actin. The contractile process stops when there are no more action potentials and no more release of
calcium from the sarcoplasmic reticulum. At this stage, the calcium in the cytosol is rapidly taken up
into the sarcoplasmic reticulum. Without calcium available to bind to troponin, tropomyosin returns to
its position of covering the myosin-binding sites on actin. When this occurs, crossbridge formation
cannot take place.

Also, as illustrated in the cycle above, the binding of ATP to the ATPase site on the myosin head is
required to separate the actin and myosin filaments at the end of a cycle.

The binding of actin to myosin
with the myosin head in the low energy configuration is called RIGOR. ATP hydrolysis is required to
move the myosin head from the low energy to the high energy configuration. Therefore, ATP must also
be available in order for muscle contraction to occur. If ATP supplies run down during prolonged
exercise this can lead to muscle fatigue and contraction will not occur even if the muscle is still being
stimulated by the motor nerve. Rigor mortis occurs after death because there is no ATP available to
separate the actin and myosin filaments. They remain in a perpetually bound state.

Question 17

When a muscle is stimulated by an action potential from a motor nerve, it undergoes a ______.

This is an increase in muscle tension in response to a single stimulus. The twitch consists of a latent
period (a delay due to the need to form crossbridges), a contraction phase in which tension increases and a relaxation phase in which tension dissipates.

A muscle can contract either isometrically or
isotonically.

Answer 17

muscle twitch

Question 18

______ is one in which the muscle is stimulated and tension develops but the muscle
does not shorten in length. This occurs when the muscle attempts to move a load that is greater than the
force that the muscle can generate. Try as hard as you can to lift a bus. Your muscles develop tension
but they do not shorten because the bus is too heavy. Your muscles cannot generate enough tension to
overcome the weight of the bus.

Answer 18

Isometric Contraction

Question 19

is one in which the muscle is able to generate enough tension to lift a load.
Tension develops and once enough tension has been developed to lift the load the muscle shortens at a constant tension.

Answer 19

Isotonic contraction

Question 20

Muscle Action Potentials and Patterns of Muscle Contraction

ONE
An action potential is quite short, approximately 5 msec in duration.

A skeletal muscle twitch is much
longer, usually over 100 msec in duration.

The graph below shows a single action potential in a muscle leading to a muscle twitch (the development of tension in the muscle).

TWO
If a second action potential arrives before the first twitch has finished, the second action potential will
trigger an increase in muscle tension that superimposes upon the initial increase in tension. This is called______ . If the action potentials arrive at a very rapid rate, tension increases significantly and
individual twitches are no longer distinguishable from one another. In this case a tension plateau is
reached. This is called _____.

Answer 20

Given that the action potential is
short and the twitch is long, many more action potentials could arrive at the muscle before the twitch
generated by the first action potential has been completed.

summation

tetanus

Question 21

tetanus

Answer 21

If the action potentials arrive at a very rapid rate, tension increases significantly and
individual twitches are no longer distinguishable from one another. In this case a tension plateau is
reached

Question 22

summation

Answer 22

f a second action potential arrives before the first twitch has finished, the second action potential will
trigger an increase in muscle tension that superimposes upon the initial increase in tension.

Question 23

A motor neuron can branch and innervate multiple muscle fibres (cells). The motor neuron and the
muscle fibres that it innervates are called a

Answer 23

motor unit

A motor neuron may innervate more than one
muscle fibre but any given muscle fibre only receives innervation from one motor neuron.

Motor units vary in size. The diagram below shows three motor units; one with a single muscle fibre;
motor unit X with 5 muscle fibres and motor unit Y with 7 muscle fibres. Muscles increase tension by
recruiting more and more motor units with smaller motor units being recruited (activated) before larger
motor units. This helps to prevent large increases in tension when they aren’t needed. For example, if
you want to pick up a pencil, you only need to recruit a few small motor units to produce enough
tension to do this. If lots of motor units were recruited then you would produce large amounts of
tension that were excessive for the task.