Professor Dave here, let’s talk about action potential.
We just learned about the structure of muscle, like skeletal muscle, which is what allows
you to move your body around.
But how exactly does this work?
If you decide to lift your arms up in the air, what is happening on the molecular level
that produces this motion?
It’s not magic, it’s just a staggering amount of chemistry, so let’s dive back
down into those muscle fibers and get a closer look.
As we recall, any skeletal muscle is made of fascicles, and each fascicle is made of
muscle fibers, which are the individual multinucleated muscle cells.
From there, we can zoom in farther on one of these myofibrils, which are in turn comprised
of myofilaments arranged into sarcomeres, and this is the contractile unit, the one
that lets muscles do what they do.
Now let’s get a closer look at these structures, because this is where all the action happens.
Looking at a sarcomere, we can label a few regions.
We can see these darker A bands and the lighter I bands, which are aligned and responsible
for the striated appearance of skeletal muscle.
Within each A band we can find a lighter region called the H zone, and this H zone is split
down the middle by something called the M line, made of a protein called myomesin.
The I bands are also split down the middle, by a region called the Z disc.
We can identify an individual sarcomere as being a section from one Z disc to the next,
and this is the functional unit of skeletal muscle.
If we zoom in even more, we can see the myofilaments that make up these regions.
As we discussed previously, the thick filaments contain myosin, and these extend across the
A band, connected at the M line.
The thin filaments contain actin, extending across the I band and into the A band.
There are also elastic filaments made of titin, spanning from the Z disc to the thick filament
and then continuing on, acting as the core of the thick filament.
Now let’s zoom in even further on these two main types of filaments.
Myosin is a protein with two globular heads pointing outwards, and a long tail which contributes
to the structure of the filament.
The heads are the site of all the activity, since there are ATP binding sites, as well
as actin binding sites, meaning this is where the thick and thin filaments will interact,
by making cross bridges.
It’s important to note the lack of myosin heads in the center of the sarcomere, just
as there also are no thin filaments.
Speaking of those, as we said, they are made predominately of actin, and two actin filaments
will twist together to form the backbone of the thin filament.
Each actin subunit has an active site where myosin can bind, and when a muscle fiber is
relaxed, these are blocked by spiraling strands of tropomyosin.
There is also troponin, a globular complex of three polypeptides, one of which binds
to actin, one of which binds to tropomyosin, and one of which binds calcium.
Beyond this, we must be aware of the sarcoplasmic reticulum, a series of tubules that surround
each myofibril.
These regulate levels of calcium, which is needed for muscle contraction, through storage
and release.
This structure includes the T tubules, which sit at each A band – I band junction, encircling
each sarcomere and helping signals reach every region of the muscle cell.
Now that we’ve examined each structural component, let’s describe how everything
works, using the sliding filament model of contraction.
This says that when the nervous system stimulates muscle fibers, the myosin heads on the thick
filaments will interact with the binding sites on the actin subunits.
These attachments will form and break several times as the thick filaments pull the thin
filaments in towards the center of the sarcomere, thus pulling the Z discs towards the M line.
The I bands shorten, and the H zone disappears.
The overall effect is that the A bands from adjacent sarcomeres get closer together, so
the entire muscle cell will shorten.
This is the mechanism by which muscles contract.
Now the question is, how is all of this activity initiated?
As we said, this begins with a signal from the nervous system.
We will examine that system in detail a bit later, but for now we can just examine the
interface between the nervous system and a skeletal muscle.
This is called the neuromuscular junction.
Each muscle fiber has one, and these sections, called axon terminals, are nearly touching
the muscle fiber, separated only by a thin space called the synaptic cleft, where the
muscle produces junctional folds within the postsynaptic membrane.
The axon terminal has lots of synaptic vesicles, which are like little bubbles, containing
acetylcholine, which is a neurotransmitter.
When a nerve impulse reaches the end of an axon, by a mechanism we will discuss later,
the axon terminal will release acetylcholine into the synaptic cleft.
The junctional folds contain acetylcholine receptors, so these will bind the approaching
acetylcholine, which causes a conformational change.
This protein will then act as an ion channel, which allows for sodium ions to enter, and
potassium ions to leave, although not in equal number.
Sodium will cross the membrane in greater quantity, and this affects the membrane potential,
or the potential difference across the membrane.
For more information on electric potential, check out my physics tutorial on this subject,
otherwise, we just need to understand that the way that positive and negative charges
are distributed within a structure can be a driving force for a particular process.
Prior to the opening of the ion channels, the inside of the cell was more negatively
charged than the outside, but as sodium ions enter, depolarization will occur.
This causes other nearby sodium channels to open, and more sodium ions will enter, following
the electrochemical gradient.
Once a particular threshold voltage is reached, this will generate an action potential.
Sodium can now diffuse into the cell anywhere along the membrane.
While this is happening, an enzyme in the synaptic cleft called acetylcholinesterase
will break down acetylcholine, and the ion channel closes, preventing further muscle
contraction until another nerve impulse arrives.
But the action potential will continue to propagate along the sarcolemma, and down the
T tubules, which opens up calcium ion release channels, which we will discuss in a moment.
Finally, after the depolarization wave has completely propagated, repolarization will
begin, due to the changes in charge density.
Potassium channels will now open, and potassium ions that are more highly concentrated within
the cell will diffuse out of the muscle fiber, which restores negative charge inside, and
the sarcolemma goes back to normal.
At this point, the muscle fiber can be stimulated again if another impulse arrives.
So we can see that charge distribution and electric potential are key concepts here,
but how does that relate to muscle contraction?
Well the action potential generated will initiate excitation-contraction coupling.
As we said, the propagation of the action potential causes a rise in levels of calcium
in the cytosol, and this is what causes the filaments to slide.
Let’s recall that when a muscle cell is relaxed, tropomyosin blocks the myosin binding
sites on the actin subunits.
But as more and more calcium ions become present, these will bind to troponin, and once two
ions bind, it will change shape, which will push tropomyosin off of the myosin binding
sites, making them available for cross bridge cycling, the process we mentioned before.
In this process, the myosin heads will pivot and bend, pulling the actin filament along
and using ATP in the process.
The two positions possible for the heads allow it to pull, detach, change position, bind,
pull, detach, and so forth, many times, until contraction is complete.
As calcium levels deplete, troponin returns to its original shape, tropomyosin blocks
actin’s binding sites once more, and the muscle fiber relaxes.
There is a lot more to discuss regarding muscle contraction.
We could talk about the time frames associated with each step in muscle contraction.
We could talk about graded muscle responses, or the differences in contraction for smooth
muscle versus skeletal.
But we will have to leave that for another day, since it’s best to really understand
the basics first.
Before moving forward, let’s quickly review what we discussed.
Muscle contraction in a skeletal muscle begins when a signal arrives at the neuromuscular junction.
Acetylcholine is released, which binds to receptors on the sarcolemma.
Sodium and potassium ions move through the ion channels, which results in a local change
in membrane voltage, also called depolarization.
This initiates an action potential, which travels across the sarcolemma in all directions,
eventually along T tubules.
This is where calcium ions are released, which interact with the myofilaments such that myosin
and actin are able to bind, and contraction begins.
Now that we understand the structure of a muscle, as well as the mechanism by which
muscles contract, let’s move forward and look at the entire muscular system as a whole,
so that we can get the big picture regarding how we move around.