describe the ultrastructure of striated muscle with reference to sarcomere structure using electron micrographs and diagrams

Control and Coordination in Mammals – Ultrastructure of Striated Muscle

Learning Objective

Describe the ultrastructure of striated (skeletal) muscle with reference to sarcomere organisation, interpret electron‑micrograph features, and explain how this structure underlies the neuro‑muscular control mechanisms required by the Cambridge International AS & A Level Biology (9700) syllabus.

1. Hierarchical Organisation of Skeletal Muscle

• Muscle fibre (cell) – multinucleated, cylindrical cell that contains many parallel myofibrils.
• Myofibril – a chain of sarcomeres arranged end‑to‑end.
• Sarcomere – the basic contractile unit, defined by two Z‑discs (≈2.2 µm long in relaxed skeletal muscle).

1.1 Myofibril Architecture

Myofibrils consist of alternating thick (myosin) and thin (actin) filaments that are anchored to specialised protein complexes at the sarcomere boundaries.

2. Detailed Sarcomere Structure

The sarcomere is divided into distinct zones (Table 1). Each zone contains characteristic proteins that give rise to the light‑and‑dark banding seen in light and electron microscopy.

2.1 Thin Filament (Actin) Details

• Polymer of G‑actin (≈1.0 µm long) arranged as a double helix.
• Tropomyosin winds around the actin helix every 7 nm.
• Troponin complex (TnC, TnI, TnT) repeats every 38.5 nm.
• Barbed (+) end attaches to the Z‑disc; pointed (–) end points toward the M‑line.

2.2 Thick Filament (Myosin) Details

• Bipolar filament ≈1.6 µm long, composed of ~300 myosin molecules.
• Each myosin molecule has two globular heads (≈10 nm) that bind ATP and actin, and a long α‑helical tail that forms the filament backbone.
• Heads project outward from the centre, creating the cross‑bridge sites.

2.3 Structural Proteins that Align the Sarcomere

• Titin – spans from Z‑disc to M‑line; acts as a molecular spring, maintaining sarcomere alignment and contributing to passive elasticity.
• Nebulin – runs along the length of the thin filament, stabilising its length and regulating actin polymerisation.
• Desmin – links adjacent myofibrils and the sarcolemma, providing overall structural integrity.

3. Muscle‑Fiber Types (Fast‑twitch vs Slow‑twitch)

Cambridge syllabus expects an understanding of how fibre type influences contraction speed, fatigue resistance and metabolic profile.

4. Ultrastructural Evidence (Electron Micrographs)

Transmission electron microscopy (TEM) provides visual confirmation of the sarcomere’s ordered architecture. Key features to identify are listed below (see Figure 1).

1. Dark, electron‑dense lines = Z‑discs (high protein concentration).
2. Uniform dark region = A‑band (densely packed thick filaments).
3. Lighter central region within the A‑band = H‑zone (absence of thin filaments).
4. Very thin central line = M‑line (myosin‑binding proteins).
5. Cross‑bridge “heads” visible where myosin attaches to actin in the overlapping zone.

5. From Structure to Function – The Neuro‑Muscular Cascade

5.1 Neuromuscular Junction (NMJ)

• Motor‑neuron terminal releases acetylcholine (ACh) into the synaptic cleft.
• ACh binds to nicotinic receptors on the motor end‑plate, opening ligand‑gated Na⁺ channels → depolarisation (end‑plate potential).
• If the end‑plate potential reaches threshold, voltage‑gated Na⁺ channels in the sarcolemma open, generating a muscle action potential.
• The action potential propagates along the sarcolemma and dives into the transverse (T‑) tubules.
• Safety factor: the NMJ produces a large end‑plate potential (≈30 mV) ensuring reliable fibre activation.

5.2 Excitation‑Contraction (E‑C) Coupling

1. Depolarisation travels down the T‑tubule system.
2. Dihydropyridine receptors (DHPR – L‑type Ca²⁺ channels) on the T‑tubule membrane undergo a voltage‑induced conformational change.
3. Mechanical coupling between DHPR and ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR) triggers rapid release of Ca²⁺ into the cytosol.
4. Ca²⁺ binds to the C‑terminal domain of troponin‑C, causing tropomyosin to shift and expose myosin‑binding sites on actin.
5. Cross‑bridge cycle (repeated for each active myosin head):

   1. Attachment: Myosin head (with ADP + Pi) binds to exposed actin site.
   2. Power stroke: Release of Pi drives the head to pivot ≈10 nm, pulling the thin filament toward the M‑line.
   3. Release of ADP: ADP dissociates, leaving the head tightly bound.
   4. Detachment: A new ATP molecule binds to the myosin head, causing it to release from actin.
   5. Cocking: ATP is hydrosed to ADP + Pi, re‑orienting the head to the high‑energy pre‑stroke position.

6. Ca²⁺ is pumped back into the SR by the Ca²⁺‑ATPase (SERCA) pump; tropomyosin re‑covers the binding sites and the muscle relaxes.

Sliding‑filament equation (Cambridge formulation):

\$\Delta L{\text{sarcomere}} = n{\text{cross‑bridges}} \times d\$

where \(d \approx 10\ \text{nm}\) is the displacement per power stroke.

5.3 Role of ATP and Calcium

• ATP is required for:

  • Detaching myosin heads from actin (cross‑bridge release).
  • Re‑cocking the myosin head (hydrolysis of ATP to ADP + Pi).
  • Operating the SERCA pump to resequester Ca²⁺.

• Ca²⁺ concentration in the cytosol rises from ~0.1 µM (rest) to >10 µM during contraction.

6. Hormonal and Autonomic Regulation

6.1 Skeletal Muscle (Sympathetic Influence)

• β‑adrenergic receptors on the sarcolemma bind adrenaline → ↑ cAMP → activation of protein kinase A (PKA).
• PKA phosphorylates glycogen phosphorylase, increasing glycogenolysis and thus ATP supply for prolonged activity.
• Sympathetic stimulation also enhances blood flow via vasodilation, supporting oxygen delivery to fast‑twitch fibres.

6.2 Cardiac Muscle

• β‑adrenergic stimulation (adrenaline) increases L‑type Ca²⁺ channel opening, raising intracellular Ca²⁺ and accelerating contraction strength and rate.
• Parasympathetic (vagal) acetylcholine reduces Ca²⁺ influx via muscarinic M₂ receptors, slowing heart rate.

6.3 Smooth Muscle

• Sympathetic (α‑adrenergic) → G‑protein‑mediated ↑ IP₃ and DAG → release of Ca²⁺ from the SR and activation of myosin light‑chain kinase (MLCK) → contraction (e.g., vasoconstriction).
• Parasympathetic (muscarinic M₂/M₃) → ↓ cAMP or ↑ NO → activation of myosin light‑chain phosphatase (MLCP) → relaxation (e.g., gastrointestinal tract).
• Hormones such as oxytocin, vasopressin and angiotensin II act via similar G‑protein pathways to modulate smooth‑muscle tone.

7. Comparison of Muscle Types

8. Clinical / Real‑World Applications

9. Summary Points

• The sarcomere, bounded by Z‑discs, is the fundamental contractile unit of skeletal muscle.
• Alternating thick (myosin) and thin (actin) filaments produce the characteristic striations visible in light and electron microscopy.
• Structural proteins (titin, nebulin, desmin) maintain alignment, elasticity and force transmission.
• Neuromuscular junction → voltage‑gated Na⁺ channels → action potential → DHPR‑RyR coupling → Ca²⁺‑dependent cross‑bridge cycling underlies voluntary contraction.
• Fast‑twitch and slow‑twitch fibres differ in myosin isoform, energy metabolism and fatigue resistance.
• Hormonal (adrenaline) and autonomic (sympathetic/parasympathetic) signals modify calcium handling and ATP provision in skeletal, cardiac and smooth muscle.
• Understanding ultrastructure explains clinical conditions such as muscular dystrophy, myasthenia gravis, the action of neuromuscular blockers and malignant hyperthermia.