Smooth Muscle Contraction | Excitation Contraction Coupling | Nerve Muscle Physiology

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 memb

rane.  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 whi

ch 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 fac

tors, 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 c

alcium 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 ent

ry 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  c

alcium 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 mus

cles 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  ph

osphorylates 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  extracellu

lar 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 myos

in'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! :)