Hello. Welcome to Byte Size Med. This video is
on how smooth muscle contracts and relaxes. To understand smooth muscle contraction, we need
to know how a skeletal muscle contracts first, and then compare. So in the next two minutes,
i'm going to very quickly go over the steps of skeletal muscle contraction, just to
give this video a little orientation. It starts at the Neuromuscular Junction. The action
potential arrives and acetylcholine is released. It acts on receptors on the muscle membrane.
Sodium enters and there's generation of an End Plate Potential. When that reaches threshold,
there's an action potential. The action potential propagates along the membrane and down the
T-tubules, which are dips from the membrane. That stimulates a Dihydropyridine Receptor, which
is a calcium channel. This channel is mechanically coupled to a Ryanodine Receptor, on the surface
of the sarcoplasmic reticulum. When that channel opens, the stored calcium exits the sarcoplasmic
reticulum and the intracellular calcium rises. The calcium binds to Troponin C, which then moves
tropomyosin out of the way, allowing myosin to bind to actin. Myosin has ATPase activity. The
energy from breaking down one molecule of ATP causes the myosin head to bend at the hinge
region, dragging the thin filament along with it. The thin filament sliding inwards shortens
the sarcomere, causing muscle contraction. The calcium ATPase pump on the surface of the
sarcoplasmic reticulum pumps calcium back into it, and once the intracellular calcium
levels come back down, the muscle relaxes. That's skeletal muscle. Now let's see how
things are different in smooth muscle. Again for contraction, smooth muscle needs calcium
in the cell to rise. But where does the calcium come from? There are different ways that that can
happen. Voltage-dependent and Voltage-independent. Voltage-dependent would be with a voltage-
sensitive channel. Here that channel is a calcium channel. Unlike skeletal muscle which has
mostly sodium channels, smooth muscles have more calcium channels. So in the action potentials of
smooth muscles, the depolarization is more from calcium entry than sodium entry. The resting
membrane potential of a smooth muscle varies. It isn't fixed. They can have spike potentials,
similar to skeletal muscles, with a few differences. Some can have action potentials with a plateau,
similar to cardiac muscles. The plateau is because the calcium channels are slow to close, versus the
sodium channels which are fast. A little side note here: these kinds of action potentials are seen
in single unit smooth muscles, which contract together as a unit. Multi-unit smooth muscles have
cells that are more independent. These cells are too small to actually have action potentials.
There's local depolarization, which creates a junctional potential that spreads through
the muscle fibre causing it to contract. So with single unit smooth muscles, there can be
spike potentials, action potentials with plateaus, and also some smooth muscles can self-generate
a slow wave rhythm, without being stimulated. So they do this on their own. Now why these waves
happen has lots of theories, but it's possibly from change in membrane permeability to ions
happening spontaneously. Calcium entering, then potassium leaving, or even from sodium entering
and leaving the cell. But these slow waves, they are not action potentials. By themselves, they
can't cause contractions. But when they do reach a threshold, there can be action potentials on
top of them. Now these can cause contraction. This is the slow wave rhythm with spikes. But the
point is that the membrane gets depolarized and that opens the voltage-gated calcium channels,
letting calcium enter into the cell. It's not just neural stimuli that control single unit
smooth muscles. Stretch can make the membrane potential less negative and generate action
potentials, causing contraction of these muscles. There are local factors, particularly with blood
vessels. Remember their walls have smooth muscles in them. If they contract, the vessel constricts.
If they relax, the vessel dilates. Local tissue environment factors like oxygen, carbon dioxide
and hydrogen ions can change what happens. Low oxygen, high carbon dioxide, high
hydrogen ions can cause the smooth muscles to relax, so that there is more blood
flow and oxygen delivery to these tissues. There are hormonal factors as well, which act on
ligand-gated calcium channels, letting calcium enter the cell. Hormones or neurotransmitters could
bind to a receptor coupled with a G-protein that can activate a second messenger, like Phospholipase
C, which is an enzyme catalyzing the hydrolysis of Phosphatidylinositol 4,5 - bisphosphate
to Inositol triphosphate, that's IP3, and Diacylglyerol. Now i know this sounds like
a big reaction, but bear with me. This IP3 has a receptor on the sarcoplasmic reticulum, allowing
the release of calcium. Calcium entry into the cell from other channels themselves, can stimulate the
release of calcium from the sarcoplasmic reticulum. That's calcium-induced calcium release.
But this IP3 mechanism is more important. However unlike skeletal muscle, where the only
source of calcium is the sarcoplasmic reticulum, in smooth muscle it's mostly the extracellular
fluid. That's because the sarcoplasmic reticulum of smooth muscle isn't very well developed. They're
located next to these little cave-like depressions on the membrane called Caveolae. These
caveolae are functionally similar to the T-tubules of skeletal muscle. Another method
by which calcium can rise is through store- operated calcium channels. When the sarcoplasmic
reticulum calcium stores come down, these channels open. In addition to replenishing the stores,
the calcium in the sarcoplasm also rises. So through any one of these methods, voltage-
dependent or independent, the calcium in the sarcoplasm rises. The next step would be for
calcium to bind to Troponin C, if we were talking about skeletal muscle. But smooth muscles don't
have troponins. What they do have is a protein called Calmodulin. So calcium binds to calmodulin
reversibly, forming a Calcium-Calmodulin Complex. Let's go back to the skeletal muscle for a bit.
They've got sarcomeres, with regularly arranged filaments. Thin filaments have actin, tropomyosin
and troponins, and the thick filaments have myosin. The thin filaments attach to a Z-disc. Now
smooth muscles do not have sarcomeres or troponin. They still do use actin and myosin though. The
actin filaments attach to dense bodies, instead of the Z-discs, and there's lesser myosin. The mechanism
of contraction still involves the sliding of the thin filaments over the thick filament. Now there's
another protein and that's called Calponin. This is usually bound to actin and tropomyosin. Now what
this does is it inhibits myosin ATPase activity, and we need that ATPase for a muscle contraction
to happen. The Calcium-Calmodulin Complex binds to Calponin and activates a protein kinase. That
phosphorylates the Calponin, so now its inhibition is removed. This complex also activates an enzyme
on the regulatory light chain of myosin, called the myosin light chain kinase. This is an important
enzyme, because in smooth muscle, myosin needs to be phosphorylated for its ATPase activity to increase,
versus skeletal muscle where it's always high. Myosin light chain kinase is a kinase, so it
phosphorylates myosin and the phosphorylated myosin is active. This can then attach to
actin so that cross-bridge cycling can happen, just like in a skeletal muscle. The hinge of myosin
bends, dragging the actin filaments along with them, resulting in a muscle contraction. So the smooth
muscle finally contracted. But how does it relax? There are calcium ATPase pumps on the sarcoplasmic
reticulum and the plasma membrane. So the calcium goes back into storage or back outside into the
extracellular fluid. There are also sodium-calcium exchangers, which send calcium out in exchange for
sodium. Through any of these methods, the calcium levels in the cell drop back down. Now the steps
reverse. Calcium gets released from calmodulin, but just that isn't enough for the muscle to
relax. The myosin is still phosphorylated. For it to become inactive again, it needs to get
de-phosphorylated. That is by another enzyme. The myosin light chain phosphatase, which removes
the phosphate from myosin's regulatory light chain and inactivates it. So the cross-bridge cycling stops
and the muscle relaxes. Smooth muscles sometimes have to sustain a force of contraction for longer
periods without rest, like to maintain the tone of blood vessels. To do that, they can't keep using up
ATP. But in these smooth muscles, the cross-bridge cycling of actin and myosin attaching, detaching
and then reattaching is slow. Actin and myosin can stay attached for longer, maintaining the tension
and so the tone without using up much energy. These are called latch-bridges and
this is the Latch-Bridge Phenomenon. Another interesting thing about smooth
muscle is the way they respond to stretch. Remember that stretch causes the muscle to
contract? So if we look at an organ like the bladder, which has smooth muscle in its walls.
When the volume increases, the stretch causes contraction, which increases the pressure. But
after a while, the tension in the muscle and so the pressure comes down. The muscle adapts to
the new length, until the volume changes again. This is called stress-relaxation. This helps organs
like the bladder store their contents temporarily. Smooth muscles can be told to contract or relax,
depending upon what the stimulus tells them to do. These are involuntary muscles. There are
neural stimuli, that's the sympathetic and the parasympathetic nervous system, hormonal
factors, neurotransmitters, and local factors. Like i mentioned earlier, depending upon what the
factor is and whether its receptor is excitatory or inhibitory, they can either cause smooth muscle
contraction or relaxation. By increasing calcium in the cell, they can cause contraction. By decreasing
it, there will be relaxation. There are also calcium- independent mechanisms, that involve changing the
rate of phosphorylation or dephosphorylation of myosin, with the two enzymes, myosin light chain
kinase and myosin light chain phosphatase. And that is some stuff about how
smooth muscles contract and relax. i hope this video was helpful. If it was
you can give it a like and subscribe to my channel for more videos like this. Thanks
for watching and I'll see you in the next one! :)