Smooth Muscle Mechanics and Adhesion

So far, I've talked a lot about things that can trigger contraction in smooth muscle, but I haven't spoken about how that contraction is actually caused. Well, now's the time!

Define dense bodies, dense bands and adherens.

Dense bodies are so-called because they look like dense, dark splotches under an electron microscope (I think). These are locations where actin filaments in the cell are cross linked with α-actinin.

Dense bands are very much like dense bodies, in that they also contain actin filaments cross-linked with α-actinin. Dense bands, however, also help form junctions between the cell and the extracellular matrix, or between the cell and other cells. These junctions are also known as adherens.

Explain the how smooth muscle cells attach to other cells and extra-cellular matrix.

As I just mentioned, junctions form at dense bands, which consist of actin filaments cross-linked with α-actinin. There are a few more proteins involved, however.

In a cell-matrix junction, actin and actinin associate with other proteins such as vinculin and talin. Talin is probably the more important one for our purposes, as it also binds to integrin. Integrin is a transmembrane protein that can connect to proteins in the extracellular matrix, such as fibronectin. Hence, integrin is sometimes known as the fibronectin receptor. In this way, actin filaments are anchored to the extracellular matrix.

In a cell-cell junction, actin and actinin still associate with vinculin, but they associate with catenin instead of talin. Catenin binds to cadherin, which, like integrin, is a transmembrane protein. Cadherin's binding site, however, is the cadherin on a neighbouring cell. Hence, cadherin serves as a "bridge" that links multiple cells together.

Recall and explain the crossbridge cycle and how it is regulated in smooth muscle.

As you may or may not know, contraction in cells relies on the movement of different filaments. Firstly, I'm going to take a step back and describe the structure of the filaments.

Thick filaments are polymers of myosin II, which has two heads. (There's also a myosin I, but that's not important for contraction. Myosin I has only one head, and it can bind and transport vesicles down actin.)

Thin filaments are polymers of actin and tropomyosin. Another fun fact to store for later (by later I mean probably a future lecture so you don't have to hold this in your head for now): monomers of actin are also known as G-actin, whereas polymers of actin are known as F-actin, or filamentous actin.

Now it's time to explain the crossbridge cycle!

Before binding can occur, the myosin head has to be in the "cocked" position. This occurs when ATPases break down ATP into ADP and Pi (phosphate). From this position, it can bind to actin, releasing a phosphate at the same time. The release of this phosphate causes a conformational change in the myosin from the cocked to the uncocked position, and it's this that causes the movement (also known as the "power stroke"). This movement triggers the release of ADP from the myosin head, which causes unbinding of myosin and actin. (Fun fact: in rigor mortis, the ADP is unable to unbind, causing stiffness.) Release of ADP also allows ATP to bind, which can then be broken down by ATPases, cocking the myosin head for the next cycle.

In smooth muscle, the rate-limiting step is the ATPase part. ATPases in smooth muscle require the regulatory light chain of myosin to be phosphorylated by myosin light chain kinase (MLCK), as mentioned here.

Explain relationship between length and tension in smooth muscle.

The optimum length for contraction occurs when myosin and actin overlap each other, allowing the maximum number of cross-bridges between the two to occur. When the muscle is made longer, less overlap occurs and less force is produced. When the muscle is made shorter, force can still be generated, but if you make the muscle too short, dense bodies might get in the way of contraction.

It's also important to note that, in smooth muscle, all of the actin/myosin combinations within the muscle are in different stages of contraction (i.e. it's not coordinated as nicely as skeletal muscle).

Define pre-load and after-load, isometric and isotonic contractions.

Pre-load and after-load have pretty much the same definitions in smooth muscle as they did in cardiac muscle. Pre-loads are loads that stretch the muscle to its starting point, and after-loads are loads that the muscle contracts against.

Isometric contractions are contractions in which the length stays the same. Just like in cardiac muscle, this is due to after-loads being too great. Muscles undergoing isometric contraction generate force without shortening.

Isotonic contractions are contractions in which the force stays the same. These may occur when there is little to no afterload, allowing the muscle to shorten without generating force.

Why does this happen? Well, force is generated when actin and myosin are bound. Muscle can't shorten when actin and myosin are bound- you need the full crossbridge cycle to occur multiple times for muscle shortening to occur. So, in short: when actin and myosin are attached, force is generated; when actin and myosin are moving, movement is generated.

Explain the relationship between force and velocity for smooth muscle in terms of crossbridge function

This is pretty much related to the point that I just made. If crossbridges are all attached and are therefore not moving, maximal force is generated, but velocity is essentially 0. As crossbridges begin to move, force decreases but velocity increases.