Hormones & Muscle Contraction
Control without wires: the endocrine system uses hormones travelling in the blood to coordinate slower, longer-lasting responses across multiple organs. Adrenaline prepares the body for immediate action in seconds — raising blood glucose, increasing heart rate, dilating airways — all via cAMP, the same second messenger that mediates glucagon signalling in the liver. And the machinery of movement: skeletal muscle's sarcomere contracts when myosin heads cycle through ATP-powered power strokes along actin filaments, controlled at every step by calcium binding to troponin and uncovering the binding sites on actin.
Nervous vs endocrine control & adrenaline
Nervous vs endocrine control — comparison
Both the nervous system (Topic 15A) and the endocrine system (Topic 14) coordinate body responses, but through fundamentally different mechanisms. The two systems often work together — the adrenal medulla is a striking example where the nervous system directly triggers hormone secretion:
| Feature | Nervous system | Endocrine system |
|---|---|---|
| Signal type | Electrical (action potentials) | Chemical (hormones in blood) |
| Speed of response | Very fast: milliseconds | Slower: seconds to minutes (or hours) |
| Duration of response | Short-lived: ceases when impulses stop | Longer-lasting: persists while hormone circulates |
| Route of transmission | Along specific neurones to precise targets | In the bloodstream to all tissues; only cells with receptors respond |
| Specificity | Highly specific: targeted to one effector | Broadly specific: hormone reaches all cells; specificity via receptor presence |
| Signal amplification | Limited (one impulse = one response) | High: one hormone molecule activates many cAMP molecules; cascade amplifies signal |
| Examples | Reflex arc; action potential propagation | Insulin, glucagon, adrenaline, ADH |
Adrenaline — secretion and the fight-or-flight response
Adrenaline (epinephrine) is a non-steroid hormone synthesised and secreted by the adrenal medulla — the inner core of the adrenal glands situated above the kidneys. Unlike most endocrine glands, the adrenal medulla is stimulated directly by the sympathetic nervous system (a branch of the autonomic nervous system), making it a neuroendocrine junction point:
- A threatening or stressful situation is perceived by the brain
- The hypothalamus activates the sympathetic nervous system
- Sympathetic nerve fibres carry impulses to the adrenal medulla
- Chromaffin cells in the adrenal medulla secrete adrenaline (and noradrenaline) directly into the bloodstream
- Adrenaline travels rapidly to all tissues in the body
Effects of adrenaline — preparing for action
Adrenaline binds to receptors on hepatocytes (liver cells), activating adenylate cyclase → cAMP → protein kinases → activation of glycogen phosphorylase → glycogenolysis (glycogen → glucose). Glucose is released into the blood, providing fuel for rapid muscle contraction and brain activity.
Adrenaline binds to receptors on the sinoatrial node (pacemaker) of the heart, increasing the rate of depolarisation → faster heart rate → more blood (oxygen and glucose) delivered to muscles and brain per minute.
Smooth muscle in the walls of bronchioles relaxes under adrenaline stimulation → airways widen → lower resistance to airflow → more oxygen can be inhaled per breath.
Arterioles leading to skeletal muscles, heart, and brain vasodilate (blood flow increases); arterioles to skin, gut, and kidneys vasoconstrict (blood flow decreases). Blood is redirected to where it is most needed for fight-or-flight.
Radial muscle of the iris contracts under adrenaline stimulation → pupils dilate → more light enters the eye → improved visual acuity for detecting threats or targets in poor light.
Adrenaline cell signalling — cAMP second messenger
Like glucagon (Topic 14), adrenaline acts via cAMP as a second messenger. As a non-steroid hormone (derived from the amino acid tyrosine), adrenaline cannot cross the plasma membrane and must use a cell-surface receptor:
- Adrenaline (first messenger) binds to a specific β-adrenergic receptor on the cell surface — a G-protein coupled receptor (GPCR)
- Receptor activates an associated G-protein, which in turn activates the enzyme adenylate cyclase (also called adenylyl cyclase) embedded in the membrane
- Adenylate cyclase converts ATP → cAMP (cyclic AMP — the second messenger)
- cAMP activates protein kinase A (PKA)
- PKA phosphorylates target enzymes: in liver cells, activates glycogen phosphorylase → glycogenolysis; in fat cells, activates lipase → lipolysis
- Blood glucose rises; adrenaline effect is short-lived — phosphodiesterase degrades cAMP to AMP, switching off the signal
Adrenaline and glucagon both use cAMP as a second messenger, yet they produce different effects (glycogenolysis via adrenaline in liver/muscle; glycogenolysis via glucagon in liver). This is because the outcome of cAMP activation depends entirely on which enzymes are present in the target cell — not on cAMP itself. The same second messenger activates different downstream pathways in different cell types. Note: insulin acts through a different receptor mechanism (not the G-protein/adenylyl cyclase/cAMP pathway required by 9700 — see Topic 14 for the glucagon cAMP pathway in detail).
Adrenaline is released by the adrenal medulla in response to stress. Which effect would NOT be expected following adrenaline secretion?
- A. Increased heart rate
- B. Glycogenolysis in the liver
- C. Dilation of arterioles to the digestive system
- D. Dilation of bronchioles
Muscle structure & sliding filament theory
Muscle tissue organisation
Skeletal (voluntary) muscle is highly organised from gross to molecular level. The unit of contraction is the sarcomere, arranged in series along myofibrils, which are bundled into muscle fibres (cells), which group into fascicles, forming the whole muscle.
| Level | Structure | Description |
|---|---|---|
| 1 (largest) | Muscle | Many fascicles bundled together; surrounded by epimysium connective tissue |
| 2 | Fascicle | Bundle of muscle fibres (cells) surrounded by perimysium |
| 3 | Muscle fibre (cell) | Single multinucleated cell; contains many parallel myofibrils; enclosed by sarcolemma; has T-tubules and sarcoplasmic reticulum |
| 4 | Myofibril | Cylinder of repeating sarcomeres; gives the cell its striated appearance under the microscope |
| 5 (smallest) | Sarcomere | Contractile unit between two Z-lines; contains interdigitating thick (myosin) and thin (actin) filaments |
Sarcomere structure — bands, zones and lines
The striated appearance of skeletal muscle under the microscope arises from the regular arrangement of filaments in each sarcomere. You must be able to identify each region and state what it contains:
| Structure | Contains | Appearance | Change during contraction? |
|---|---|---|---|
| Z-line | Protein disc anchoring the thin (actin) filaments at each end of the sarcomere | Dark line; marks boundaries of the sarcomere | Z-lines move closer together — sarcomere shortens |
| A-band | Entire length of myosin (thick) filaments; includes the region of overlap with actin | Dark band | Does NOT change length — myosin filaments do not move relative to M-line |
| I-band | Only actin (thin) filaments — the non-overlapping region at each end of the sarcomere | Light band; bisected by Z-line | Shortens/disappears as actin slides in |
| H-zone | Only myosin (thick) filaments — the central region not overlapped by actin | Lighter region within A-band | Shortens/disappears as actin slides in and overlaps more of myosin |
| M-line | Protein disc anchoring myosin filaments in the centre of the sarcomere | Dark line in centre of H-zone | Remains in centre; unchanged |
- Shortens: I-band, H-zone, sarcomere length (Z-lines closer)
- Stays the same: A-band (myosin filament length unchanged), myosin filament length, actin filament length
- The filaments themselves do NOT shorten — they slide past each other. This is the essence of the sliding filament theory.
Filament proteins
Each myosin molecule has a double-headed structure. The myosin head (globular ATPase domain) binds actin and hydrolyses ATP to power the power stroke. The tail portions bundle together to form the thick filament backbone.
The thin filament is built around a double-stranded chain of actin molecules. Wound around the actin helix are two regulatory proteins: tropomyosin (long filamentous protein that blocks the myosin-binding sites on actin) and troponin (a complex that holds tropomyosin in position and contains the binding site for Ca²⁺). Titin is a large elastic protein that connects myosin to the Z-line and maintains sarcomere architecture during stretching.
Sliding filament theory — the cross-bridge cycle
Muscle contraction occurs because actin filaments slide toward the centre of the sarcomere, pulled by the cyclic action of myosin heads. This is driven by ATP hydrolysis and regulated by Ca²⁺:
- Calcium release: an action potential arrives at the muscle fibre (via the neuromuscular junction); it propagates along the sarcolemma and down T-tubules into the interior of the cell; this triggers the release of Ca²⁺ from the sarcoplasmic reticulum (SR) into the sarcoplasm
- Troponin binding: Ca²⁺ binds to troponin on the thin filament; troponin changes shape
- Tropomyosin moves: the shape change in troponin causes tropomyosin to shift along the actin filament, exposing the myosin-binding sites on actin
- Cross-bridge formation: the myosin head (which has already hydrolysed ATP → ADP + Pₙ, and is now in its “cocked” high-energy position) binds to the exposed site on actin — forming a cross-bridge
- Power stroke: the myosin head pivots (bends) toward the M-line, pulling the actin filament toward the centre of the sarcomere; ADP and Pₙ are released during this stroke
- Detachment: a new ATP molecule binds to the myosin head, causing it to release from actin (detach from the cross-bridge)
- Re-cocking: the myosin head hydrolyses ATP → ADP + Pₙ; the energy released returns the head to its “cocked” high-energy position, ready to form a new cross-bridge further along the actin filament
- Steps 4–7 repeat for as long as Ca²⁺ is present and ATP is available → actin slides inward → sarcomere shortens → muscle contracts
- Ca²⁺: without Ca²⁺, tropomyosin remains in position blocking myosin binding sites; no cross-bridges form; no contraction regardless of ATP availability
- ATP: without ATP, detachment of the myosin head from actin is impossible; the muscle remains locked in a contracted “rigor” state (rigor mortis in death is caused by exhaustion of ATP in muscle cells)
Muscle relaxation
Relaxation is not passive. When action potentials stop arriving:
- Ca²⁺ is actively pumped back into the SR by Ca²⁺-ATPase pumps (requiring ATP)
- Ca²⁺ concentration in the sarcoplasm falls
- Ca²⁺ dissociates from troponin; troponin reverts to its original shape
- Tropomyosin slides back over the myosin-binding sites on actin
- No new cross-bridges can form; existing cross-bridges detach as ATP binds to myosin heads
- The sarcomere extends back to its resting length (aided by elastic tissue, the opposing muscle group, and titin)
Which correctly describes changes in the bands of a sarcomere during contraction?
- A. A-band shortens; I-band and H-zone stay the same
- B. All bands shorten proportionally
- C. I-band and H-zone shorten; A-band stays the same length
- D. A-band and H-zone shorten; I-band stays the same
Explain the role of calcium ions and ATP in muscle contraction, referring to troponin, tropomyosin, and the myosin cross-bridge cycle. [8]
- Ca²⁺ is released from the sarcoplasmic reticulum (SR) when an action potential arrives; its concentration in the sarcoplasm rises [1]
- Ca²⁺ binds to troponin on the thin filament; troponin changes shape [1]
- The shape change causes tropomyosin to shift along the actin filament, exposing the myosin-binding sites on actin [1]
- The myosin head (already in the high-energy “cocked” position with ADP + Pₙ bound) binds to the exposed site — cross-bridge formation [1]
- The power stroke: myosin head pivots/bends, pulling actin toward the M-line; ADP and Pₙ released [1]
- A new ATP molecule binds to the myosin head, causing detachment from actin [1]
- ATP is hydrolysed (ATPase activity of myosin head) to ADP + Pₙ; myosin head returns to high-energy cocked position [1]
- The cycle repeats as long as Ca²⁺ is present, exposing binding sites, and ATP is available; actin slides inward; sarcomere shortens [1]
- Without ATP, the myosin head cannot detach from actin — muscle remains contracted (rigor) [1]
- When stimulation stops, Ca²⁺ is actively pumped back into SR; tropomyosin covers binding sites again; cross-bridges cannot reform; muscle relaxes [1]
The neuromuscular junction
The neuromuscular junction (NMJ) is the synapse between a motor neurone and a skeletal muscle fibre. It is structurally and functionally analogous to a cholinergic synapse (Topic 15A), with one important difference: the postsynaptic cell is not another neurone but a muscle fibre.
NMJ structure
The axon terminal of the motor neurone. Contains mitochondria, synaptic vesicles filled with acetylcholine, and voltage-gated Ca²⁺ channels. Essentially identical to the presynaptic terminal of a cholinergic synapse.
~20–50 nm gap between nerve terminal and muscle fibre membrane. Contains acetylcholinesterase (AChE), which rapidly breaks down ACh to terminate the signal. Basement membrane bridges the gap.
The specialised region of the muscle fibre membrane (sarcolemma) that faces the motor nerve terminal. Highly folded (junctional folds) to increase surface area. Contains nicotinic ACh receptor proteins that, when bound by ACh, open Na⁺ channels.
NMJ transmission — from nerve impulse to muscle contraction
- Action potential arrives at the motor nerve terminal (axon knob)
- Voltage-gated Ca²⁺ channels open; Ca²⁺ enters the terminal
- ACh-filled vesicles fuse with the presynaptic membrane by exocytosis; ACh released into the cleft
- ACh diffuses across the cleft and binds to nicotinic receptors on the motor end plate of the muscle sarcolemma
- Chemically-gated Na⁺ channels open; Na⁺ enters the muscle fibre
- Localised depolarisation of the sarcolemma (end-plate potential, EPP) — this is large enough to always trigger an action potential in the muscle fibre (unlike at neurone-to-neurone synapses, where summation may be needed)
- Action potential propagates along the sarcolemma in both directions from the NMJ
- Action potential enters the T-tubules (invaginations of the sarcolemma deep into the muscle fibre)
- T-tubule depolarisation triggers Ca²⁺ release from the adjacent sarcoplasmic reticulum
- Ca²⁺ in the sarcoplasm binds troponin → tropomyosin moves → myosin binding sites exposed → cross-bridge cycle begins → muscle contracts
- ACh in the cleft is hydrolysed by acetylcholinesterase; depolarisation ceases when action potentials stop; Ca²⁺ pumped back into SR; muscle relaxes
NMJ compared to a neurone-to-neurone synapse
| Feature | Neurone-to-neurone cholinergic synapse | Neuromuscular junction (NMJ) |
|---|---|---|
| Neurotransmitter | Acetylcholine | Acetylcholine |
| Presynaptic cell | Neurone | Motor neurone |
| Postsynaptic cell | Neurone (or gland cell) | Skeletal muscle fibre |
| Postsynaptic specialisation | Dendrite or cell body | Motor end plate (junctional folds) |
| Summation needed to fire? | Usually yes — multiple EPSPs needed | No — one EPP is always enough to trigger an AP in the muscle fibre |
| Signal termination | AChE breaks down ACh | AChE breaks down ACh |
| Second messenger | Not usually for direct electrical response | T-tubule → SR Ca²⁺ release (intracellular pathway after AP) |
One motor neurone may innervate hundreds to thousands of muscle fibres. When a single action potential arrives, hundreds of vesicles release ACh simultaneously, producing a very large EPP — typically 5–10 times the threshold potential. This guarantees that every nerve impulse produces a muscle contraction (“twitch”). Summation is not required at the NMJ — unlike at neurone-to-neurone synapses.
Topic 15B Practice — Comprehensive
Mixed practice across hormones, muscle contraction, and the NMJ.
Adrenaline acts on liver cells to raise blood glucose. Which correctly describes the intracellular signalling mechanism?
- A. Adrenaline enters the hepatocyte and directly activates glycogen phosphorylase
- B. Adrenaline binds to a nuclear receptor, activating transcription of glycogen phosphorylase genes
- C. Adrenaline binds to a surface receptor, activating adenylate cyclase, which produces cAMP; cAMP activates protein kinases that activate glycogen phosphorylase
- D. Adrenaline directly phosphorylates glycogen phosphorylase on the cell surface
A student observes a contracted sarcomere under the electron microscope. Which observation correctly indicates that the sarcomere is contracted compared with a relaxed state?
- A. The A-band is shorter than in the relaxed state
- B. The I-band is shorter and the H-zone has disappeared compared with the relaxed state
- C. The actin filaments are shorter than in the relaxed state
- D. The Z-lines have disappeared and the sarcomere boundary is lost
A student is startled by a loud noise. Within seconds, their heart rate increases, blood glucose rises, and their pupils dilate.
(a) Name the hormone responsible for these effects and state where it is secreted. [2]
(b) Explain why this hormone, despite affecting many tissues simultaneously, cannot be described as non-specific. [2]
(c) Describe the intracellular mechanism by which this hormone raises blood glucose in liver cells. [4]
(a) Hormone and source [2 marks]
- Hormone: adrenaline (epinephrine) [1]
- Secreted by the adrenal medulla (inner core of adrenal glands, above kidneys) [1]
(b) Why not non-specific despite wide distribution [2 marks]
- Adrenaline travels in the bloodstream and reaches all tissues, but only cells with the specific β-adrenergic receptor (or α-adrenergic receptor) on their cell surface respond [1]
- Specificity is conferred by the receptor — the same hormone can produce different responses in different cells depending on which receptor type and downstream enzymes are present [1]
(c) Intracellular mechanism in liver cells [4 marks]
- Adrenaline binds to a β-adrenergic receptor (GPCR) on the hepatocyte surface membrane [1]
- The receptor activates adenylate cyclase (via a G-protein), which converts ATP to cAMP (cyclic AMP) [1]
- cAMP activates protein kinase A (PKA), which phosphorylates target enzymes [1]
- Phosphorylation activates glycogen phosphorylase → glycogenolysis: glycogen is broken down to glucose-1-phosphate → glucose → released into bloodstream, raising blood glucose [1]
Describe the sequence of events from an action potential arriving at a neuromuscular junction to the shortening of sarcomeres in the muscle fibre. [9]
- Action potential arrives at motor nerve terminal; voltage-gated Ca²⁺ channels open; Ca²⁺ enters terminal [1]
- ACh vesicles fuse with presynaptic membrane by exocytosis; ACh released into synaptic cleft [1]
- ACh diffuses across cleft; binds to nicotinic ACh receptors on motor end plate of muscle fibre sarcolemma [1]
- Chemically-gated Na⁺ channels open; Na⁺ enters; sarcolemma depolarises (end-plate potential) [1]
- Action potential generated in sarcolemma; propagates along sarcolemma and down T-tubules into muscle fibre interior [1]
- T-tubule action potential triggers Ca²⁺ release from sarcoplasmic reticulum into the sarcoplasm [1]
- Ca²⁺ binds to troponin on thin filaments; troponin changes shape; tropomyosin shifts to expose myosin-binding sites on actin [1]
- Myosin head (in cocked high-energy position with ADP+Pi bound) binds exposed site on actin — cross-bridge formed [1]
- Power stroke: myosin head pivots toward M-line, pulling actin inward; ADP and Pi released [1]
- New ATP binds myosin head → detachment; ATP hydrolysed → head re-cocked; cycle repeats → sarcomere shortens; I-band and H-zone reduce in length [1]
Topic 15B — Common Mistakes
- 🔨Saying the A-band shortens during contractionThe A-band does NOT shorten. It represents the entire length of the myosin filament, which does not change in length. Only the I-band and H-zone shorten. Candidates who say "all bands shorten" lose marks. Memorise: A-band stays; I-band and H-zone shrink.
- 💥Saying actin or myosin filaments shortenThe fundamental point of the sliding filament theory is that the filaments do NOT change length — they slide relative to each other. The sarcomere shortens because of increased overlap, not because of filament shortening. This is the most common sliding filament misconception.
- 🧬Confusing the role of troponin and tropomyosinTropomyosin blocks the myosin-binding sites on actin (the physical blocker). Troponin holds tropomyosin in position and contains the Ca²⁺ binding site. When Ca²⁺ binds troponin, it changes shape, which moves tropomyosin aside. Don't say "Ca²⁺ binds tropomyosin" — it binds troponin.
- ⚡Saying muscle contraction does not require ATP once cross-bridges formATP is required at EVERY step of the cross-bridge cycle: to detach the myosin head from actin, to re-cock the head, and (via Ca²⁺-ATPase) to pump Ca²⁺ back into the SR for relaxation. Rigor mortis occurs precisely because ATP is exhausted and myosin heads cannot detach. "Muscle contraction uses ATP" but relaxation also uses ATP.
- 📌Saying adrenaline enters cells to act directly on enzymesAdrenaline is a polar, water-soluble amine — it cannot cross the hydrophobic plasma membrane. It acts via a surface receptor (GPCR) → G-protein → adenylate cyclase → cAMP second messenger. Saying "adrenaline enters the cell and activates glycogen phosphorylase" is wrong.
- 🌟Saying the nervous system and endocrine system never work togetherThe adrenal medulla is a classic example of integration: the sympathetic nervous system (nerve impulses) directly stimulates the adrenal medulla to release adrenaline (a hormone). The two systems are deeply interconnected, not independent. The NMJ is another example: nerve impulses at the NMJ trigger hormonal-like intracellular Ca²⁺ signalling in the muscle.
- 👥Saying the NMJ requires summation to fire a muscle action potentialWrong. At the NMJ, one action potential releases enough ACh to produce an end-plate potential (EPP) large enough to fire an action potential in the muscle fibre without summation. This is different from neurone-to-neurone synapses, where summation is usually required. The NMJ is all-or-nothing at the level of the motor unit.
- 💥Confusing T-tubules and sarcoplasmic reticulumT-tubules (transverse tubules) are invaginations of the sarcolemma that carry the action potential deep into the muscle fibre. The sarcoplasmic reticulum (SR) is the specialised smooth ER that surrounds the myofibrils and stores Ca²⁺. The action potential in the T-tubule triggers Ca²⁺ release FROM the SR. They are adjacent structures with linked functions, not the same structure.
- 🧠Forgetting the M-line and Z-line when describing sarcomere structureBoth are required for a complete sarcomere diagram or description. Z-line: anchors actin at sarcomere ends (marks sarcomere boundary). M-line: anchors myosin at the sarcomere centre. Many candidates draw actin and myosin filaments correctly but omit these anchor structures, losing structural marks.
- 🌟Saying adrenaline is a steroid hormoneAdrenaline is a catecholamine derived from the amino acid tyrosine — it is a non-steroid, water-soluble hormone that cannot cross the plasma membrane. Steroid hormones (e.g. cortisol, testosterone) are lipid-soluble and can enter cells directly to bind nuclear receptors. The signalling pathway is completely different.
Topic 15B completes the control chapter. Highest-yield items: 7-row nervous vs endocrine comparison table, adrenaline secreted by adrenal medulla via sympathetic NS stimulation, adrenaline cAMP signalling (GPCR → adenylate cyclase → cAMP → PKA → glycogenolysis), sarcomere band changes during contraction (A-band constant / I-band + H-zone shorten), cross-bridge cycle 8 steps with Ca²⁺ and ATP roles, troponin binds Ca²⁺ / tropomyosin moves / binding sites exposed, NMJ complete sequence (ACh → EPP → T-tubule AP → SR Ca²⁺ release → contraction), rigor from ATP absence. Synoptic links: Topic 14 (cAMP — same second messenger for glucagon and adrenaline; insulin uses a different mechanism), Topic 14.3 (Ca²⁺-ATPase analogous to Na⁺/K⁺-ATPase), Topic 15A (action potential → NMJ, ACh mechanism), Topic 12A (ATP from respiration fuels myosin ATPase and Ca²⁺ pump).