describe the roles of neuromuscular junctions, the T-tubule system and sarcoplasmic reticulum in stimulating contraction in striated muscle

Control and Coordination in Mammals – A‑Level Biology 9700

Learning Objective

Describe the roles of the neuromuscular junction, the T‑tubule system and the sarcoplasmic reticulum in stimulating contraction in striated (skeletal) muscle, and explain how these structures fit into the wider nervous, endocrine and homeostatic control of the body.

1. The Three Interacting Control Systems

The Cambridge syllabus expects you to understand how the following systems cooperate to produce and regulate movement:

• Nervous system – rapid electrical signalling (resting and action potentials, synaptic transmission, reflex arcs).
• Endocrine system – slower, chemical signalling via hormones that modulate the sensitivity and capacity of muscle fibres.
• Feedback & homeostasis – negative‑feedback loops that maintain internal stability (e.g. blood‑pressure, blood‑glucose and calcium regulation).

In muscle contraction the nervous system provides the initial trigger, the endocrine system adjusts the strength and duration of the response, and feedback mechanisms ensure that the response does not overshoot the physiological set‑point.

2. Nervous‑System Details Required by the Syllabus

2.1 Resting membrane potential of a skeletal‑muscle fibre

2.2 Generation of an action potential

• Voltage‑gated Na⁺ channels open → rapid Na⁺ influx → depolarisation.
• Voltage‑gated K⁺ channels open later → K⁺ efflux → repolarisation.
• Na⁺/K⁺‑ATPase restores the ionic gradients (3 Na⁺ out, 2 K⁺ in per ATP).

2.3 Propagation along the axon

• Myelinated axons: saltatory conduction, 80–120 m s⁻¹.
• Unmyelinated fibres: continuous conduction, 0.5–2 m s⁻¹.

2.4 General synaptic transmission

• Action potential reaches the presynaptic terminal → voltage‑gated Ca²⁺ channels open.
• Ca²⁺ influx triggers vesicular release of neurotransmitter into the synaptic cleft.
• Neurotransmitter binds to postsynaptic receptors → ion channels open → postsynaptic depolarisation (excitatory) or hyperpolarisation (inhibitory).

2.5 Reflex arcs – example

Monosynaptic stretch reflex: muscle‑spindle → sensory neuron → spinal cord → motor neuron → same muscle contracts. This illustrates rapid, involuntary control of skeletal muscle.

3. Neuromuscular Junction (NMJ)

3.1 Structure

• Presynaptic motor‑neuron terminal containing synaptic vesicles loaded with acetylcholine (ACh).
• Synaptic cleft (~50 nm) filled with basal lamina.
• Postsynaptic motor end‑plate on the sarcolemma, densely packed with nicotinic acetylcholine receptors (nAChRs).

3.2 Sequence of events

1. Action potential arrives at the motor‑neuron terminal.
2. Voltage‑gated Ca²⁺ channels open → Ca²⁺ influx.
3. Ca²⁺ triggers exocytosis of ACh‑containing vesicles.
4. ACh diffuses across the cleft and binds nAChRs.
5. nAChR activation opens Na⁺ (and a small Ca²⁺) channel → end‑plate potential (EPP, ≈ +30 mV).
6. If the EPP reaches threshold, a muscle‑action potential is generated on the sarcolemma.

3.3 Key quantitative data

4. T‑Tubule System

4.1 Structure & triad

• T‑tubules are invaginations of the sarcolemma that run perpendicular to the fibre axis.
• Each T‑tubule is flanked on either side by a terminal cisterna of the sarcoplasmic reticulum, forming a triad (T‑tubule + 2 SR cisternae).

4.2 Functional roles

• Electrical coupling – the surface action potential spreads into the T‑tubules, ensuring simultaneous depolarisation of the fibre interior (≈ 1 ms for a 5 mm fibre).
• Mechanical coupling – voltage‑sensitive dihydropyridine receptors (DHPRs, L‑type Ca²⁺ channels) in the T‑tubule membrane are physically linked to ryanodine receptors (RyRs) on the SR.
• Triggering Ca²⁺ release – depolarisation moves the S4 segment of DHPRs, which pulls on RyRs and opens their Ca²⁺ channels.

4.3 Quantitative note

Typical T‑tubule diameter ≈ 50 nm; spacing between adjacent triads ≈ 2 µm in fast‑twitch fibres, providing a dense network for rapid signal transmission.

5. Sarcoplasmic Reticulum (SR)

5.1 Structure

• Network of membranous tubules surrounding each myofibril.
• Terminal cisternae (part of the triad) store the bulk of releasable Ca²⁺.

5.2 Calcium handling

• Storage concentration – ≈ 1 mM Ca²⁺ inside the SR lumen.
• Resting cytosolic concentration – ≈ 100 nM (≈ 10⁴‑fold lower).
• Release – RyR channels open, Ca²⁺ diffuses into the myoplasm (peak [Ca²⁺] ≈ 10 µM within < 1 ms).
• Re‑uptake – SERCA (sarco(endo)plasmic reticulum Ca²⁺‑ATPase) pumps Ca²⁺ back at ≈ 5 µmol kg⁻¹ s⁻¹, using ATP.
• Buffering – troponin C binds Ca²⁺ (K_d ≈ 4 µM) to translate the signal to the contractile proteins.

5.3 Quantitative summary

6. Integrated Sequence: From Nerve Impulse to Muscle Contraction

1. Motor neuron fires an action potential (≈ 80 m s⁻¹ in a myelinated axon).
2. Voltage‑gated Ca²⁺ channels open in the presynaptic terminal → Ca²⁺ influx.
3. ACh is released into the synaptic cleft and binds nAChRs on the motor end‑plate.
4. Na⁺ (and a small Ca²⁺) influx generates an end‑plate potential; if threshold is reached, a muscle‑action potential propagates along the sarcolemma.
5. The action potential enters the T‑tubule system.
6. DHPRs sense the depolarisation and mechanically open RyRs in the adjacent SR terminal cisternae.
7. Ca²⁺ rushes from the SR into the cytosol (rise from 100 nM to ≈ 10 µM within < 1 ms).
8. Ca²⁺ binds to troponin C → conformational change moves tropomyosin, exposing myosin‑binding sites on actin.
9. Cross‑bridge cycling (ATP‑dependent) produces sliding of actin over myosin → fibre shortens (contraction).
10. When neural stimulation ceases, SERCA pumps Ca²⁺ back into the SR, cytosolic Ca²⁺ falls, tropomyosin re‑covers the binding sites and the fibre relaxes.

7. Summary Table of Key Components

8. Suggested Diagram (for exam revision)

A labelled cross‑section of a skeletal muscle fibre should show:

• Motor‑neuron terminal and synaptic cleft (NMJ).
• Motor end‑plate with nAChRs.
• Sarcolemma with invading T‑tubules.
• Triad (T‑tubule flanked by two SR terminal cisternae).
• Myofibrils with actin and myosin filaments.
• Arrows indicating the direction of the action potential and Ca²⁺ flow.

9. Key Equation (optional – deeper insight)

The change in intracellular Ca²⁺ concentration during a twitch can be expressed as:

\$\$

\Delta[Ca^{2+}] = \frac{J{\text{release}} - J{\text{uptake}}}{V_{\text{cell}}}

\$\$

• J_release – flux of Ca²⁺ from the SR (µmol L⁻¹ s⁻¹).
• J_uptake – flux back into the SR via SERCA.
• V_cell – cytosolic volume of the fibre.

Typical values for a fast‑twitch fibre: J_release ≈ 5 µmol L⁻¹ s⁻¹ and J_uptake ≈ 4.5 µmol L⁻¹ s⁻¹ during the first 100 ms of a twitch.

10. Feedback & Homeostasis Involving Skeletal Muscle

10.1 Baroreceptor reflex (blood‑pressure control)

• Increased arterial pressure stretches carotid‑sinus baroreceptors → ↑ afferent firing to the medulla.
• Medulla increases parasympathetic outflow (↓ heart rate) and reduces sympathetic outflow to skeletal‑muscle vasculature → vasodilation.
• Reduced peripheral resistance lowers blood pressure, illustrating a negative‑feedback loop that also influences muscle perfusion.

10.2 Blood‑glucose regulation (non‑muscle example)

• High blood glucose → β‑cells release insulin → ↑ glucose uptake by muscle (GLUT4 translocation) and liver → blood glucose falls.
• Low blood glucose → α‑cells release glucagon → ↑ hepatic glucose output → blood glucose rises.
• Both hormones indirectly affect muscle performance by altering substrate availability.

10.3 Calcium homeostasis (non‑muscle example)

• Low plasma Ca²⁺ → parathyroid hormone (PTH) released → ↑ bone resorption, ↑ renal Ca²⁺ re‑absorption, ↑ activation of vitamin D → ↑ intestinal Ca²⁺ absorption.
• High plasma Ca²⁺ → calcitonin released from thyroid C‑cells → ↓ bone resorption.
• These loops keep extracellular Ca²⁺ within a narrow range, ensuring sufficient Ca²⁺ is available for muscle contraction.

11. Endocrine Control Relevant to Muscle Function

• Adrenaline (epinephrine) – binds β₂‑adrenergic receptors (G_s) → ↑ cAMP → PKA phosphorylates DHPRs, enhancing Ca²⁺ release and contractile force.
• Insulin – stimulates GLUT4 translocation → ↑ glucose uptake → more ATP for SERCA and cross‑bridge cycling.
• Thyroid hormones (T₃/T₄) – increase synthesis of myosin heavy chains and mitochondrial enzymes, improving endurance.
• Parathyroid hormone (PTH) – raises extracellular Ca²⁺, indirectly supporting muscle contraction.

12. Assessment / Extension Questions

1. Explain how the T‑tubule system ensures that the action potential reaches every myofibril within a skeletal muscle fibre, and why this is essential for a coordinated contraction.
2. Describe the dual role of the sarcoplasmic reticulum in contraction and relaxation, including the key pumps and channels involved.
3. Draw and label a diagram that shows the complete pathway from acetylcholine release at the NMJ to cross‑bridge cycling, indicating the flow of ions and the major protein players.
4. Discuss how a negative‑feedback loop involving baroreceptors and the autonomic nervous system helps maintain blood pressure during vigorous muscle activity.
5. Compare the actions of adrenaline and insulin on skeletal muscle, focusing on their effects on Ca²⁺ handling and ATP availability.

13. Quick Audit of the Notes Against the Cambridge Syllabus (Topic 15 – Control and Coordination)