A Review of Basic Muscle Physiology

Now we're onto skeletal muscle!

Gross and cellular structure of skeletal muscle

Muscle consists of muscle fibres (which are just muscle cells with a fancy name). Several muscle fibres wrapped in perimysium form a fascicle. Blood vessels run between fascicles.

Muscle fibres contain numerous myofibrils, which take up most of the space in the cell. The mitochondria, sarcoplasmic reticulum etc. just get squished up in between. The numerous nuclei are pushed to the outside of the cell.

Myofibrils are made up of thick and thin filaments, which form a banded appearance under a microscope. These produce contraction.

Structure and arrangement of the contractile filaments (the sarcomere)

Thin filaments consist of actin, tropomyosin and troponin. Actin makes up the bulk of the thin filament, tropomyosin covers the myosin binding sites on actin and troponin binds to and moves tropomyosin out of the way when it's time to allow contraction to take place.

Thick filaments in skeletal muscle are pretty much the same as those in smooth muscle (i.e. they are made up of myosin II). The tails of myosin filaments meet together in the middle of the thick filament, with the heads at either end. There is a small section in the middle that has only tails and is thus known as the "bare zone."

Thick and thin filaments are arranged in structures called sarcomeres. At either end of a sarcomere is a Z disc. Thin filaments bind to this Z disc and extend towards the centre of the sarcomere from either side. Thick filaments are located in the middle of the sarcomere, and are held in place by the M-line. There is some overlap between thick and thin filaments. The area containing the thick filament is called the A band, or "dark" band, as it looks dark under a microscope. The area containing only thin filaments (i.e. the bits where the thin filaments do not overlap the thick filaments) is called the I band, or "light" band. The area containing thick filaments only (i.e. no overlap with thin filaments) is also known as the H band.

There are other proteins within the sarcomere. Titin connects the M-line to the Z-line and is responsible for muscle elasticity. Nebulin wraps around actin and regulates its length.

How the contractile filaments interact to produce contraction (the sliding filament theory)

As I just mentioned above, the myosin heads are located at either end of the thick filament. These "heads" can bind to actin and pull it inwards over the myosin filament, causing contraction. This is known as the sliding filament theory (don't be fooled by the word "theory"- it's pretty well established). During contraction, the A band stays constant (as myosin doesn't change in length), but the I and H bands shorten due to increased overlap.

How skeletal muscle contraction is controlled

Contraction of skeletal muscle, just like in smooth muscle, requires cross-bridges to cycle. Cross-bridge cycling of skeletal muscle works pretty much the same way as smooth muscle. The main difference here is that the phosphorylation of the regulatory light chain is not the limiting step here: instead, it's tropomyosin.

As I mentioned earlier, tropomyosin can block the myosin binding sites of actin. When Ca²⁺ comes in, tropomyosin can be moved away from the myosin binding site, allowing binding and contraction to occur.

The effect of stimulation frequency of force output

When single action potentials are given, one at a time, the muscle produces a single twitch. When a few action potentials are given one after the other, a phenonemon called "twitch summation" occurs: subsequent twitches are larger than the first. (This isn't purely additive though: two action potentials won't create twice as much tension.) When a lot of action potentials are given, a large amount of tension is created for a long period of time (a state called "tetanus," which is the most well-known symptom of the disease with the same name).

Twitch summation occurs even though the amount of calcium influx is the same in all cases. To understand why this happens, we need to understand what happens when calcium is in the cell. Ca²⁺ can bind to troponin C, creating a Ca-Troponin C complex which is ultimately what moves the tropomyosin filament. The binding of calcium to troponin is relatively slow compared to the release. Hence, for a reasonable amount of Ca-Troponin complexes to form, calcium needs to be in the cell for a reasonable amount of time. If there are more action potentials, calcium can stay in the cell longer, forming more Ca-Troponin complexes. This results in more movement of tropomyosin away from the binding sites and thus more force generated.

The relationship between muscle length and force output

As you stretch a muscle, the basal force (minimum force produced) increases, but the active force (the difference between maximum and minimum force) decreases. This occurs for several reasons:

• At the optimal muscle length, all of the myosin heads are in close proximity with actin, allowing the maximum number of crossbridges to form. This produces the maximum amount of force.
• At longer muscle lengths, there is less overlap between myosin and actin filaments, so fewer crossbridges can form and less force can be produced.
• At very long muscle lengths, actin and myosin no longer overlap so no force can be produced.
• At shorter muscle lengths, actin filaments from either side get pushed over each other. This pushes the filament on one side closer to the myosin, and the filament on the other side further away from the myosin. When actin is pushed too far away from myosin, crossbridges cannot form, reducing the force.
• At very short muscle lengths, the myosin filaments run into the Z discs, preventing contraction from occurring at all.

The mechanisms responsible for graded contractions in skeletal muscle

When a muscle contracts, not all of it contracts at once. A single motor neuron will only activate a certain number of fibres. This set-up is known as a "motor unit." The amount of contraction generated by a muscle as a whole depends on how many motor units are activated. Usually, smaller motor units (i.e. motor neurons that only activate a small number of fibres) are activated first, allowing for fine control.