Skeletal Muscle

Our second topic in Veterinary Physiology 1 is all about muscle. This post will discuss skeletal muscle. 

Structure 

Skeletal muscle is composed of muscle fibres which are muscle cells. These fibres, when bound together, are known as fascicles. Fascicles are surrounded by connective tissue, this connective tissue gathers together at the end of a muscle to form the tendon. The tendon connects muscle to bone. 

Muscle fibres contain:

• A cell membrane known as a sarcolemma
• A sac like storage area for Ca 2+ ions called a sarcoplasmic reticulum
• multiple nuclei
• a rod like contractile element called a myofibril
• T (transverse) Tubules which are invaginations of the plasma membrane and penetrate deep into the cell.
• a rod like contractile unit called a myofibril

Myofibrils consist of sarcomeres which line up along the long axis of the cell. Sarcomeres are the contractile units of the myofibril. Sarcomeres are made up of:

• Thin filaments: responsible for contraction and are composed of:
• A contractile protein - actin
• Regulatory proteins - tropomyosin and troponin
•  Thick filaments: also responsible for contraction and are composed of:
• myosin which is composed of two intertwining subunits, each with a 'head'
• The head of the myosin subunit has an actin binding site and an ATPase site
• Two myosin molecules join tail to tail then form filaments with other myosin molecules with heads protruding in an orderly helical pattern. 
• Titin: the largest known protein
• The titin molecule connects the M line to the Z line.
• It stabilises the position of the contractile filaments
• Its elastic recoil helps the muscle return to its resting length after contraction.
• A Z-line which defines the end of a sarcomere and anchors actin filaments.
• An M-line which marks the middle of the sarcomere and anchors the myosin filaments.  

The Structure of a Sarcomere

This website has excellent diagrams which show the structure of skeletal muscle. It also has an alternative explanation of what I'll be discussing below - it's definitely a very useful resource 


Mechanisms of Contraction:


Excitation:


Skeletal muscle requires synaptic activation from a synaptic neuromuscular junction to contract (this is described as neurogenic). Skeletal muscle fibres are innervated by a single motor neuron. A single motor neuron innervates many muscle fibres. A motor unit is a motor neuron and all the muscle fibres it innervates. It is the functional unit of skeletal muscle.

Excitation-Contraction Coupling:

This consists of all the events which occur between the firing of a muscle Action Potential (AP) and the start of contraction. 

1. An AP is fired in a muscle cell
2. The AP spreads along the sarcolemma and down the T-tubules
3. This activates the dihydropyridine receptors (which are voltage gated), which opens the ryanodine receptors, which are Ca 2+ channels on the sarcoplasmic reticulum (SR).
4. The calcium ions released bind to troponin which displaces tropomyosin from myosin binding sites on the actin molecules.
5. This allows contraction (cross bridge cycling) to occur, which is dependent on the release of Ca 2+ from intracellular stores.

 Contraction:

Sliding filament theory: during contraction the lengths of thick and thin filaments do not change. Instead they slide past each other which shortens the length of the sarcomere. During isotonic contraction, the muscle will produce enough force to lift a weight after which this force will stay the same and the muscle will shorten. During isotonic contraction, the length of the muscle doesn't change, the filaments shorten but the elastic elements lengthen causing the muscle to stay the same length.

But how do the thick and thin filaments actually slide past each other? This occurs through crossbridge cycling. This occurs in 5 stages:

1. Myosin binds to actin
2. Power stroke: the myosin head pulls the actin molecule along
3. Rigor: the actin and myosin are tightly bound. This occurs in the absence of ATP
4. Myosin detaches from actin: this requires ATP input
5. Cocking of myosin head: ATP hydrolysis releases energy which 'cocks' the head and primes it for movement.

This cycle can then repeat to contract the muscle further.

This website has a useful diagram which shows this process in a picture form.  
Relaxation:    
Crossbridge cycling occurs as long as cytoplasmic Ca 2+ is present. If Ca 2+ levels drop Ca 2+ dissociates from troponin causing tropomyosin to cover the myosin binding sites on actin molecules. Calcium ions are removed from the thick and thin filaments by a Ca-ATPase pump which pumps Ca2+ ions into the sarcoplasmic reticulum against the concentration gradient. The elastic recoil of the titin molecules helps the muscle return to its resting length.  

Factors Affecting the Strength of Muscle Contraction

Several factors can be used to increase the strength of muscle contraction:

• Frequency of stimulation: Muscle fibres can fire many APs during a single twitch. Repeated APs can cause more Ca 2+ to be released than can be used. Therefore, an increase in the frequency of AP firing can lead to more frequent Ca2+ release from the SR. This leads to a higher level of cytoplasmic calcium ions which results in more cross bridge cycling. This generates more force.  
• Fibre diameter: the more sarcomeres are present in parallel, the more force can be generated. Therefore bulkier muscles are stronger. 
• The force of muscle contraction depends on the length of the muscle before contraction starts. Stretching changes the overlap between actin and myosin filaments.

 The nervous system can also determine the force that a muscle produces by recruiting more motor units. The more motor units are recruited, the more force will be generated. Motor units may vary in size (in terms of the number of muscle fibres per neuron). Small motor units fire first while large muscle units fire last, this enables fine motor control. 


Types of Skeletal Muscle Fibres

Fast-Twitch


Fast twitch muscle fibres contract relatively quickly and contain fast myosin. They rapidly hydrolyse ATP which leads to fast crossbridge cycling. They are glycolytic fibres which generate ATP more rapidly through glycolysis, which is anaerobic. However, they fatigue rapidly due to the build up of lactic acid. They usually have a large diameter, few capillaries, few mitochondria and they lack myoglobin. They are white in colour.


Slow-Twitch

Slow twitch muscle fibres contract relatively slowly, and contain slow myosin. They hydrolyse ATP more slowly which leads to fewer crossbridge cycles being completed each second. They are oxidative fibres which generate ATP by oxidative phosphorylation, which is aerobic and allows them to resist fatigue. They are smaller in diameter and contain many capillaries, mitochondria and contain myoglobin. They are red in colour.