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.
