explain the sliding filament model of muscular contraction including the roles of troponin, tropomyosin, calcium ions and ATP

Control & Coordination – Sliding Filament Model

Learning outcomes (what you need to know)

• Describe how a motor‑neuron impulse initiates skeletal‑muscle contraction (ACh → NMJ → action potential → excitation‑contraction coupling).
• Explain how hormones and the autonomic nervous system modulate cardiac and smooth‑muscle activity.
• Compare excitation‑contraction coupling in skeletal, cardiac and smooth muscle.
• Outline the sliding‑filament model, naming the key proteins (actin, myosin, troponin, tropomyosin) and ions (Ca²⁺, ATP) and using the exact Cambridge terminology.
• Detail each stage of the cross‑bridge cycle, using the syllabus wording “high‑energy myosin head”, “power stroke”, “cross‑bridge detachment”, etc.
• Quantify the mechanical output of one ATP hydrolysis event and relate it to macroscopic shortening of a fibre.
• Design a simple experiment to investigate the calcium‑force relationship and interpret the data.
• Identify the main proprioceptive feedback mechanisms that fine‑tune muscle force.

1. Overview of “Control & Coordination”

Movement and internal homeostasis are regulated by three interacting levels:

1. Neural control – motor‑neuron action potentials, neurotransmitter release at the neuromuscular junction (NMJ), reflex arcs and proprioceptive feedback.
2. Hormonal & autonomic control – catecholamines, acetylcholine, noradrenaline, vasopressin, etc., which modify the activity of cardiac and smooth muscle.
3. Feedback mechanisms – muscle spindles, Golgi tendon organs, baroreceptors and chemoreceptors that provide information to the CNS and generate negative‑feedback loops.

2. Neural signalling to skeletal muscle

1. Motor‑neuron impulse travels down the axon to the NMJ.
2. Acetylcholine (ACh) is released into the synaptic cleft, binds to nicotinic receptors on the sarcolemma, opening ligand‑gated Na⁺ channels → end‑plate potential.
3. The depolarisation spreads along the sarcolemma and down the T‑tubule system.
4. Voltage‑sensitive L‑type Ca²⁺ channels (dihydropyridine receptors) undergo a conformational change that mechanically couples to ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR).
5. RyR open, releasing Ca²⁺ from the SR into the cytosol – the first step of excitation‑contraction coupling.

3. Hormonal & autonomic regulation

3.1 Cardiac muscle

• Calcium‑induced calcium release (CICR) – a small influx of Ca²⁺ through L‑type channels triggers massive Ca²⁺ release from the SR via RyR.
• Troponin C (cardiac isoform) has a higher affinity for Ca²⁺ than the skeletal isoform, allowing rapid activation.
• Autonomic influence:

  • β‑adrenergic stimulation (adrenaline, noradrenaline) → ↑ cAMP → enhanced L‑type Ca²⁺ entry → positive inotropy (stronger contraction) and positive chronotropy (faster heart rate).
  • M‑type cholinergic stimulation (vagus nerve) → ↓ cAMP → negative inotropy and chronotropy.

• Intercalated discs contain gap junctions that allow the action potential to spread rapidly from cell to cell, ensuring a coordinated contraction.

3.2 Smooth muscle

• Ca²⁺ binds to calmodulin, forming a Ca²⁺‑calmodulin complex.
• The complex activates myosin light‑chain kinase (MLCK), which phosphorylates the regulatory light chain of myosin, converting the head into the high‑energy state.
• Phosphorylated myosin heads bind to actin, perform a power stroke and then detach when dephosphorylated by myosin light‑chain phosphatase (MLCP).
• Regulation is primarily through autonomic neurotransmitters:

  • Sympathetic α₁‑adrenergic → ↑ IP₃ → Ca²⁺ release from the SR → contraction.
  • Parasympathetic muscarinic → ↓ Ca²⁺ or ↑ cAMP → relaxation.
  • Hormones such as vasopressin, endothelin, and angiotensin II also raise intracellular Ca²⁺.

3.3 Feedback mechanisms (syllabus requirement)

• Muscle spindles – stretch receptors in skeletal muscle that detect changes in length and send afferent signals to the spinal cord, producing a stretch reflex that increases motor‑neuron firing.
• Golgi tendon organs – tension receptors located in tendons; high tension triggers an inhibitory reflex that reduces motor‑neuron activity, protecting the muscle from damage.
• Baroreceptors (carotid sinus & aortic arch) – monitor blood pressure; increased pressure → vagal stimulation → ↓ heart rate; decreased pressure → sympathetic stimulation → ↑ heart rate and contractility.
• Chemoreceptors – detect changes in O₂, CO₂ and pH; stimulate respiratory and cardiovascular adjustments that indirectly affect muscle performance.

4. Sliding‑filament model – Skeletal muscle

4.1 Key proteins & ions (syllabus terminology)

4.2 Cross‑bridge cycle (step‑by‑step, syllabus wording)

1. Excitation‑contraction coupling – action potential travels along the sarcolemma and T‑tubules, causing Ca²⁺ release from the SR.
2. Ca²⁺ binding – Ca²⁺ binds to the C‑terminal EF‑hand of TnC.
3. Conformational change – the troponin‑tropomyosin complex moves, uncovering the myosin‑binding sites on actin.
4. Cross‑bridge formation – a high‑energy myosin head (bound to ADP + Pᵢ) attaches to actin.
5. Power stroke – release of ADP and Pᵢ causes the myosin head to pivot, pulling the thin filament ≈5 nm toward the M‑line.
6. ATP binding – a new ATP molecule binds to the myosin head, causing detachment from actin.
7. ATP hydrolysis – myosin‑ATPase hydrolyses ATP → ADP + Pᵢ, re‑cocking the head into the high‑energy position.
8. Relaxation – when neural stimulation stops, Ca²⁺ is pumped back into the SR by the Ca²⁺‑ATPase (SERCA). Troponin returns to its Ca²⁺‑free conformation, tropomyosin re‑covers the binding sites and the fibre relaxes.

4.3 Quantitative note (AO1)

• One ATP hydrolysis powers a single power stroke that moves the actin filament ≈5 nm (0.005 µm).
• A typical skeletal‑muscle fibre contains ~10⁴ sarcomeres in series; to shorten the fibre by 1 mm ≈ 2 × 10⁵ cross‑bridge cycles are required per filament.
• During intense activity, skeletal muscle can consume ≈ 1 mol ATP kg⁻¹ min⁻¹.

4.4 Summary table – Cross‑bridge cycle

5. Practical application – Calcium‑force relationship (AO2)

Objective: Investigate how increasing extracellular Ca²⁺ concentration affects the twitch force of a skinned skeletal‑muscle fibre.

Analysis (AO2): The force rises sharply as Ca²⁺ concentration increases because more Ca²⁺ binds to the C‑terminal sites on TnC, shifting tropomyosin and allowing additional cross‑bridges to form. At ≈5 µM the binding sites become saturated – virtually all TnC molecules are occupied – so further increases in Ca²⁺ produce little or no additional force, giving the characteristic plateau.

6. Linking the model to whole‑body control

• The CNS adjusts the firing frequency of motor neurons; a higher frequency releases more ACh, producing a larger Ca²⁺ transient and therefore a greater number of active cross‑bridges – a direct neural‑to‑molecular link.
• During exercise, adrenaline raises cardiac output and also enhances Ca²⁺ entry into cardiac cells, increasing stroke volume – a systemic feedback loop that illustrates “control & coordination”.
• Proprioceptive feedback (muscle spindles & Golgi tendon organs) constantly informs the CNS about muscle length and tension, allowing rapid adjustments of motor‑neuron firing to maintain posture and prevent injury.