The Neuromuscular System (Part 5) – Skeletal Muscle Structure & Contraction (NM Junction & Excitation Contraction Coupling)

Hopefully you are now familiar with basic anatomy of the brain, spinal cord, the various neurons that reside within the tracts and how they communicate with eachother. In this article, we will aim to discuss how neurons communicate with skeletal muscle fibers and the processes preceding contraction.

To understand how nerve cells meet with skeletal muscle, the basic structure of a muscle should be understood. Muscles are generally split into 3 categories:

  1. Cardiac – As easily distinguished from the name, this is the muscle of the heart and is involuntary i.e. they are provided neural communication via the autonomic nervous system (ANS).
  2. Smooth – Found within the walls of organs and responsible for a significant level of elasticity. Once again, controlled by the ANS (involuntary) and examples include: blood vessels, digestive tract and eyes.
  3. Skeletal – Attached to the skeletal system to enable movement and stability. Morphologically distinct from cardiac and smooth due to it’s striated appearance (fibers) and is voluntarily controlled through the somatic nervous system.

Let us break down the architecture of a whole skeletal muscle numerically (the larger the number, the more internal):

Figure 1. Overall structure of skeletal muscle; from muscle belly to sarcomere.
  1. Epimysium – Bundles of muscle are connected to the bone via tendons and wrapped by a fascia of fibrous connective tissue.
  2. Perimysium – A single bundle of the many, is then individually protected by an additional sheath of connective tissue. These bundles may be named in some anatomy texts as ‘fasciculi‘.
  3. Endomysium – An individual bundle (fascicle) contains thousands of muscle fibers and each of these fibers are also wrapped in a layer of connective tissue.
  4. Muscle fiber – These are the cylindrical cells of the muscle which extend from the tendon of origin to the tendon of insertion. A single fiber may contain up to a 100 nuclei therefore it is a multinucleated cell.
  5. Sarcolemma – The cell membrane of an individual muscle fiber. Like many cells, the role of the sarcolemma is to maintain a barrier between intracellular and extracellular compartments while allowing through ions and water via the specific ions pumps and aquaporin channels.
  6. T-tubules – A unique feature of the sarcolemma is it’s penetration into the sarcoplasm (cytoplasm of the muscle cell) via membranous tubules running down longitudinally. These are known as T-tubules and are enclosed on either side via terminal cisternae (enlargements).
  7. Sarcoplasmic reticulum – The terminal cisternae extend out towards smooth endoplasmic reticulum (known as sarcoplasmic reticulum in muscle cells) and have the role of storing and releasing calcium ions. They are also part of the sarcoplasm within which proteins (e.g myoglobin). glycogen and fat droplets and other small molecules/ions are found.
  8. Myofibrils – The tubules, cisternae and sarcoplasmic reticulum all surround the main contractile structure of a fiber. These are known as myofibrils and come in large quantities, densely packed in parallel fashion and forming the bulk of an individual fiber.
  9. Sarcomere – Each myofibril consists of thick and thin protein filaments in uniform fashion. The structure is repeated consistently across the whole length of the myofibril, only separated by a thin membrane labelled as the ‘Z-Line‘. A sarcomere is the grouping of these thick and thin filaments from one Z-line to the next, and aligns with sarcolemma via costameres (found at the Z-line also).
Figure 2. Detailed breakdown of individual muscle fiber; outlining the T-tubules, terminal cisternae and sarcoplasmic reticulum.

The action point for the majority part of skeletal muscle contraction, occurs within the myofibril (particularly at the level of the sarcomere), so let us delve slightly further into the structure and zones of the myofibril. Much of the studies related to myofibrils and sarcomeres have been based on electron/light microscopy, voltage-sensitive dyes and other optic techniques, hence some of the structures will refer to their methods of discovery/observation.

Figure 3. Bands/zones of an individual sarcomere + microscopic view.

Within the centre of each resting sarcomere lies a dark line (in microscopic view) consisting of the thick & thin protein filaments; this is known as the A-band. Based on the optical property of the tissue, the A stands for anisotropic. At the centre of the A-band, the area within which thick filaments reside, is called the H-zone (in reference to Hensen who discovered it). Spanning across both ends of two Z-disks, wherein only thin filaments are found, is the I-band. Microscopically, these are lighter bands and stand for isotropic. As mentioned earlier, each sarcomere is separated by a thin membrane (Z-lines/disks) and like a disk, cuts the myofibril into individual units. The Z refers to ‘zwischen’ (German for ‘in between), as the Z-disk sits in the centre of the I-band and in between each sarcomere.

The basic contractile elements in skeletal muscle are primarily based upon 4 proteins:

  1. MyosinThick myofilament making up for ~50% of protein within the myofibril. It consists of two heavy chains wrapped against eachother, forming 2 globular heads that stick out of these chains. The head structures are responsible for a) affinity to actin for binding and b) facilitating ATPase activity. Each pair of heads along a myosin chain is said to sit 120degrees rotated from it’s neighbouring pair (Figure 4).
  2. ActinThin myofilament accounting for 20-25% of myofribillar protein. A double helix consisting of 2 chains of monomers twisted around eachother (similar to two strings of beads). They attach to the Z-disks and are responsible for moving in towards eachother during contraction.
  3. Tropomyosin – Found at the thin filament and plays a regulatory role in allowing/breaking actin and myosin interaction. Two strands across the double helix chain of actin; with each rod-like molecule of tropomyosin, ~7 actin monomers are found in direct contact, blocking the pathway for myosin bonding.
  4. Troponin – Also found at the thin filament, sitting beside every tropomyosin molecule and is essentially responsible for switching tropomyosin on or off, therefore a regulatory protein. Troponin comes in 3 subunits: a) TN.C – calcium binding protein, b) TN.I – stops actin-myosin interaction (inhibitory) and c) TN.T – this binds very strongly to tropomyosin, facilitating actin-myosin interaction.
Cross bridge 1
Figure 4. Actin and myosin interaction during contraction. Note that myosin heads rotate as they go along.

How does contraction occur?

Now that we have all the pieces of the puzzle in front of us, it’s time to put it together to create the big picture!

Neuromuscular Junction:

As mentioned in the previous article, an excitatory action potential may occur and travel along down a motor axon which synapses with another dendrite OR in this case: a few skeletal muscle fibers. Chemical synapses have a gap between their presynaptic cells and postsynaptic cells known as the synaptic cleft, but the connection of this lower motor neuron to the muscle is called the neuromuscular junction, and the region at which the axon has terminated is now called the motor end plate.

At the motor axon, Acetylcholine (Ach) is being locally synthesized and is the primary neurotransmitter at every NM junction.

Important fact: At the NM junction, as Ach is the only neurotransmitter, inhibition or lesser contractions at the muscle is only the result of less Ach release or Ach inhbition.

So as an action potential travels through the axon:

  1. Ach is synthesized from Acetyl coenzyme A (CoA) and choline, and then incorporated into it’s membrane bound vesicles.
  2. Ca2+ voltage gated channels open due to the depolarization of axon terminal (Na+ influx). Ca2+ influx leads to phosphorylation of synapsins and allows vesicles to travel to presynaptic membrane.
  3. Release of Ach via exocytosis and vesicles fuse with presynaptic membrane.
  4. Ach binds with post synaptic nicotinic Ach (fast) receptors (refer to the previous article if unsure)
  5. This leads to a conformational change in the ligand gated channels, specifically leading to Na+ influx into the muscle cell and susbsequently depolarizes the muscle cell.
  6. Acetyl-cholinesterase (enzyme) sweeps into dissociate and hydrolyse the used Ach from the post synaptic receptors. This ensures rapid clearance in preparation for further action potentials.
NM Junction2
Figure 5. Step by step breakdown of an action potential at the NM junction.

How does this now translate to the skeletal muscle?

Simply put: the end result of adequate excitatory action potentials upon a muscle results in contraction whereby the muscle tends to ‘shorten’ in length. But upon the entry of Na+ and therefore, a depolarizing current within the muscle fiber, what actually happens next?

  1. The action potential now travels through the sarcolemma in to the T-tubules, whereby it can now activate the release of Ca2+ from the terminal cisternae.
  2. This flow of Ca2+ enters the sarcoplasmic reticulum (part of the sarcoplasm) allowing the exposure of Ca2+ to the thin and thick filaments. (REMEMBER: At rest, the sarcoplasm is free of Ca2+).
  3. Two Ca2+ ions attach themselves to each calcium binding site of Troponin (T.C).
  4. The binding of Ca2+ leads to the movement of tropomyosin rods from the periphery towards the centre, whereby they are no longer blocking myosin heads from attaching to an actin monomer.
  5. Myosin heads (containing an Adenosine diphophate compound [ADP] and inorganic phosphate [P]) move out and upwards towards an actin binding site creating a cross-bridge formation.
  6. The myosin heads pivot and pull the actin filament towards the midline or middle of the A-band. This is called the power stroke. As this occurs, ADP and P now leave the myosin head and contraction has occured.
  7. The myosin is still attached and therefore the muscle cannot relax UNTIL a new ATP attaches to myosin head and allows for its’ detachment from actin.
  8. The hydrolysis of this ATP leads to the ‘cocking back’ of the myosin heads, leaving it with ADP and P again, in preparation for the next contraction or returning to a rested state.
  9. ATP is also hydrolyzed in the process of actively transporting Ca2+ ions (1 ATP for 2 Ca2+ ions) back to the cisternae. This now means that tropomyosin has returned to blocking each actin monomer from myosin cross-bridging.
Figure 6. Excitation contraction coupling process within 6 steps (excluding the removal of Ca2+ ions).

Something to remember: This is the action of a SINGLE pair of myosin heads within a sarcomere. A muscle such as the bicep may contain up to a 100 000 sarcomeres!

This whole process has been given the term ‘excitation–contraction coupling’ (ECC) which was first named by Alexander Sandow in 1952 and it aims to describes the rapid communication between electrical and chemical events leading to a muscle contraction. Hopefully this section will have done that process to a relevant level of detail, though it is actually much more complex than this! More can be understood in this review (

That concludes my summary of skeletal muscle structure and contraction for today! Stay tuned for the following articles/topics within the NM System series:

  • Motor Units – Recruitment & Synchronization.
  • Neurological adaptations to training.

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