3.6.1

Stimuli and response

Stimuli, detection and response 3.6.1.1

Stimuli, detection and response (Stimuli, detection and response)
Definitions
  • Stimulus: a detectable change in an organism's internal or external environment.
Notes
  • The general pathway from stimulus to response — stimulus → receptor (specific detection) → coordinator (integration) → effector (e.g. muscle or gland) → response — is the same basic framework underlying every specific example covered in this topic, from a simple reflex to hormonal control of blood glucose.
  • Responding appropriately to stimuli has direct survival value: detecting and moving toward a favourable resource (or away from a harmful one), or reacting fast enough to avoid injury, directly affects an organism's chances of survival and reproduction.

Plant tropisms and auxin (IAA) 3.6.1.1

Plant tropisms (Stimuli, detection and response)
Definitions
  • Tropism: a directional growth response of a plant toward or away from a directional stimulus, brought about by differential (unequal) cell elongation on either side of the responding organ.
Key results
  • Phototropism (shoot, positive): IAA (auxin) accumulates on the shaded side → greater cell elongation on that side → the shoot bends toward the light.
  • Gravitropism: in a shoot (negative), IAA accumulates on the lower side, promoting greater elongation there, so the shoot bends upward; in a root (positive), IAA accumulates on the lower side too, but at root concentrations it INHIBITS elongation, so the lower side elongates less and the root bends downward.
Notes
  • IAA moves away from growing regions (e.g. a shoot tip) and regulates differential cell elongation wherever it accumulates unevenly — an uneven IAA distribution, not an uneven light or gravity stimulus directly, is what actually causes the differential growth.
  • The single most important, most commonly mistested fact here: IAA has OPPOSITE effects on roots and shoots at a given concentration — the same hormone, redistributed identically by gravity to the lower side in both organs, promotes elongation in a shoot but inhibits it in a root. This is why gravitropism bends a shoot upward and a root downward using the same underlying mechanism.
  • Roots respond to (are inhibited by) much lower IAA concentrations than the concentrations that promote shoot elongation — the dose-response relationship is genuinely different between the two organs, not just a coincidence of which side has more auxin.

Taxes and kineses 3.6.1.1

Simple movement responses (Stimuli, detection and response)
Definitions
  • Taxis: a directional movement response toward (positive) or away from (negative) a directional stimulus.
  • Kinesis: a non-directional response in which the RATE of movement or turning changes with stimulus intensity, without the movement itself being directed toward or away from the stimulus source.
Notes
  • The key distinction is directionality, not simply whether movement occurs: in taxis, the organism actively orients and moves toward or away from the stimulus source (e.g. positive chemotaxis, moving toward a chemical source); in kinesis, movement speed or turning rate changes with local stimulus intensity, but individual movements are not aimed at or away from the source at all.
  • A kinesis response can still be effective at moving an organism toward more favourable conditions overall (e.g. moving faster and turning less in unfavourable dry air, moving slower and turning more in favourable moist air, so the organism spends more net time in moist regions), even though no single movement is itself directed — the favourable outcome emerges statistically from many undirected movements, not from active orientation.

The reflex arc 3.6.1.1

A three-neurone reflex (Stimuli, detection and response)
Key results
  • A simple reflex pathway: stimulus → receptor → sensory neurone → (relay neurone, in the spinal cord/CNS) → motor neurone → effector — e.g. a pain receptor detecting a pinprick, relayed through the spinal cord, triggering muscle contraction and withdrawal.
Notes
  • A reflex is rapid and involuntary specifically because the pathway is short (as few as three neurones) and does not require conscious processing in the brain — the relay neurone in the spinal cord is sufficient to connect sensory input directly to a motor response.
  • This short pathway is exactly what gives a reflex its survival value: it protects the body from harm faster than a response requiring full conscious decision-making could.
  • Synapses between the neurones in a reflex arc work identically to any other synapse in the nervous system — a reflex arc's speed comes from its short, simple route, not from any special synaptic mechanism unique to reflexes.

Receptors: the Pacinian corpuscle and the retina 3.6.1.2

The Pacinian corpuscle · Rods and cones (Stimuli, detection and response)The Pacinian corpuscle (Stimuli, detection and response)Rods and cones (Stimuli, detection and response)
Definitions
  • Generator potential: a graded change in membrane potential, produced by a receptor in response to a stimulus, whose size increases with stimulus strength — triggers an action potential only if it depolarises the membrane to threshold.
Key results
  • Pacinian corpuscle: pressure change deforms the lamellae → opens stretch-mediated Na⁺ channels in the sensory neurone ending → Na⁺ influx produces a graded generator potential — a stronger effective stimulus produces a bigger generator potential and, once threshold is reached at the axon, a higher action-potential frequency (never a bigger action potential).
  • Rods: high sensitivity to light, but low visual acuity and no colour discrimination, due to a high degree of convergence (many rods connecting to one bipolar/ganglion cell, summing their signals). Cones: require brighter light, but provide high visual acuity and colour vision (three pigment types), due to low convergence — especially at the fovea, which contains only cones.
Notes
  • The Pacinian corpuscle shows rapid adaptation to a maintained (unchanging) pressure — its generator potential (and so its action-potential firing) declines even while the pressure itself continues, which is why you stop consciously noticing constant pressure (e.g. from clothing) shortly after it is first applied.
  • Light HYPERPOLARISES rods and cones (the opposite of how most other receptors work, which typically depolarise in response to their stimulus) — a genuinely distinctive feature of visual phototransduction worth remembering explicitly.
  • Convergence trades spatial resolution for sensitivity: summing many rods' weak individual signals into one output neurone makes the combined signal detectable in dim light, but means the brain cannot tell exactly which of the many contributing rods was stimulated — hence rods give high sensitivity but low acuity, and the low-convergence, fovea-concentrated cones give the reverse trade-off.

Control of heart rate 3.6.1.3

Control of heart rate (Stimuli, detection and response)
Definitions
  • Myogenic: describes cardiac muscle's ability to initiate its own electrical activity intrinsically, without requiring an external nerve impulse to start each contraction.
Key results
  • Intrinsic control: the sinoatrial node (SAN, the heart's pacemaker) initiates a wave of electrical excitation that spreads across both atria → the atrioventricular node (AVN) picks this up after a short delay (allowing the atria to finish emptying before the ventricles contract) → the excitation passes along the Bundle of His and Purkyne tissue, causing ventricular contraction that spreads from the apex (bottom) of the heart upward.
  • Extrinsic (autonomic) control: pressure receptors (in the carotid sinuses and aortic arch) detect arterial stretch, and chemoreceptors (in the carotid and aortic bodies, plus central sensing of CSF pH) detect blood CO₂, H⁺ and O₂ — sensory neurones relay this information to the cardiovascular centres in the medulla oblongata, which adjust heart rate via the sympathetic system (noradrenaline, increases SAN rate) or the parasympathetic system (vagus nerve, acetylcholine, decreases SAN rate).
Notes
  • Insulating tissue around the AVN and the Bundle of His ensures the wave of excitation can ONLY reach the ventricles via this one controlled pathway — without it, excitation could spread from the atria to the ventricles directly and uncoordinated, rather than being routed and delayed exactly where needed.
  • Ventricular contraction spreading from the apex upward (rather than from the top down) is what actually squeezes blood effectively up and out through the arteries at the top of the ventricles — the direction of the spreading wave of excitation is functionally important, not an incidental detail.
  • Higher arterial pressure → increased receptor firing → increased vagal (parasympathetic) drive → decreased heart rate; lower arterial pressure produces the opposite chain — a direct negative-feedback loop stabilising blood pressure via heart rate.
  • During physical activity, raised CO₂ and lower blood pH (detected by chemoreceptors) contribute to an increased heart rate, on top of any pressure-based signal — both pressure and chemical signals feed into the same cardiovascular centres and combine to set the final heart rate at any moment.

Worked examples

Worked example 3.6.1 · 5 marks

A shoot is illuminated from one side only.

After several hours, the shoot is observed to have bent toward the light source.

Explain this observation in terms of the distribution and effect of IAA (indoleacetic acid), and predict what would happen if the tip of the shoot (where IAA is produced) were removed before the shoot was illuminated from one side.

Show worked solution

IAA is transported laterally toward the shaded side, giving a higher concentration there than on the illuminated side.

IAA stimulates cell elongation, so the shaded side elongates more, curving the shoot toward the light.

If the tip were removed, no IAA would be produced, since production occurs specifically in the growing tip — without it, both sides would elongate similarly and little or no bending would occur.

Mark scheme · 5 marks

  • States IAA accumulates on the shaded side 1 mark
  • States IAA stimulates cell elongation 1 mark
  • Explains greater elongation on the shaded side causes bending toward the light 1 mark
  • Predicts removing the tip prevents IAA production 1 mark
  • States without IAA production, little or no bending would occur 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

Worked example 3.6.1 · 5 marks

A Pacinian corpuscle is subjected to two separate pressure stimuli: stimulus A is a light, brief touch; stimulus B is a firmer, more prolonged press.

Explain, in terms of the generator potential produced, why stimulus B produces a higher frequency of action potentials in the associated sensory neurone than stimulus A, even though the amplitude of any single action potential produced is identical in both cases.

Show worked solution

A firmer stimulus deforms the lamellae more, opening more stretch-mediated Na⁺ channels and producing a larger generator potential for B than A.

A generator potential is graded (varies with stimulus strength), so a larger one exceeds threshold more often, giving a higher frequency of action potentials for B.

Amplitude does not vary, since action potentials are all-or-nothing — stimulus intensity is encoded through frequency alone.

Mark scheme · 5 marks

  • States stimulus B produces a larger generator potential 1 mark
  • States the generator potential is graded, varying with stimulus strength 1 mark
  • Links a larger generator potential to a higher frequency of threshold-crossing 1 mark
  • States action potential amplitude is fixed (all-or-nothing principle) 1 mark
  • States stimulus intensity is encoded by frequency, not amplitude 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

Worked example 3.6.1 · 5 marks

During moderate exercise, a person's heart rate increases significantly above its resting value.

Explain the sequence of events, starting from the detection of a relevant change during exercise, that brings about this increase in heart rate, naming the receptors, nerves and heart structures involved.

Show worked solution

Increased CO₂ concentration is detected by chemoreceptors, which send impulses via sensory neurones to the cardiovascular centre in the medulla.

This increases sympathetic impulses to the SAN, which increases its rate of spontaneous excitation.

This wave still spreads across the atria, through the AVN, and along the bundle of His and Purkyne tissue, but more frequently per minute.

Mark scheme · 5 marks

  • States chemoreceptors detect rising CO₂ concentration 1 mark
  • States impulses travel to the cardiovascular centre in the medulla 1 mark
  • States increased sympathetic impulses reach the SAN 1 mark
  • States the SAN increases its rate of spontaneous excitation 1 mark
  • States the wave still passes via the AVN, bundle of His and Purkyne tissue, now more frequently 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

3.6.2

Nervous coordination

Motor neurone structure 3.6.2.1

Myelinated motor neurone (Nervous coordination)
Notes
  • A motor neurone's dendrites and cell body receive and integrate synaptic input before any resulting impulse travels along the axon toward the axon terminals — integration happens at the initial segment (trigger region), where the combined input either does or does not reach threshold.
  • The myelin sheath (formed by Schwann cells) insulates the axon, interrupted at regular gaps called nodes of Ranvier — these nodes contain a high density of voltage-gated ion channels, the structural basis for saltatory conduction covered in the next section.

Resting and action potentials 3.6.2.1

Resting potential and the action potential (Nervous coordination)
Definitions
  • All-or-nothing principle: every action potential in a given neurone reaches the same peak, since the rising phase is a positive feedback loop that runs to completion once triggered, regardless of how far past threshold the original stimulus was.
Key results
  • Resting potential (typically about −70 mV, inside negative relative to outside) is maintained by the Na⁺/K⁺ pump (3 Na⁺ out : 2 K⁺ in, using ATP) plus the membrane's much greater resting permeability to K⁺ than Na⁺ via K⁺ leak channels.
  • Action potential sequence: threshold reached → voltage-gated Na⁺ channels open, Na⁺ influx causes depolarisation (further opening more Na⁺ channels, a positive feedback loop) → peak at about +30 mV → Na⁺ channels inactivate, voltage-gated K⁺ channels open, K⁺ efflux causes repolarisation → K⁺ channels close slightly late, causing a brief hyperpolarisation → resting potential is restored.
Notes
  • The absolute refractory period (Na⁺ channels have not yet recovered from inactivation) makes a further action potential completely impossible for a brief interval; the relative refractory period that follows (some Na⁺ channels have recovered) still allows a new action potential, but only with a stronger-than-normal stimulus.
  • Refractoriness sets an upper limit on action-potential firing frequency, and also helps keep normally initiated impulses travelling in one direction along an axon, since the just-fired membrane immediately behind an active region cannot re-fire straight away.
  • Because a single action potential's amplitude never varies (all-or-nothing), stimulus intensity can only be encoded by firing FREQUENCY in one neurone, or by how many neurones are recruited — never by the size of any individual spike.

Propagation of action potentials 3.6.2.1

Propagation along an axon (Nervous coordination)
Key results
  • Unmyelinated axon: local currents from an active (depolarised) region spread to, and depolarise, the immediately adjacent resting region to threshold, regenerating the action potential there — continuous conduction, one adjacent patch of membrane at a time.
  • Myelinated axon: myelin prevents local current loss along insulated stretches, so depolarisation effectively jumps from node of Ranvier to node of Ranvier, regenerating full action potentials only at each node — saltatory conduction.
Notes
  • Saltatory conduction is substantially faster than continuous conduction precisely because action potentials only need to be actively regenerated at the widely spaced nodes, rather than at every adjacent patch of membrane along the entire axon length.
  • Conduction speed also increases with greater axon diameter (lower internal resistance to local current flow) and with higher temperature (within the normal physiological range, faster ion channel kinetics) — myelination, diameter and temperature are three genuinely independent factors affecting speed, not different descriptions of the same thing.
  • The refractory period immediately behind an actively firing region (already active, briefly unable to re-fire) is part of what ensures propagation proceeds in one direction only, away from the point of initiation, in both conduction types.

Synaptic transmission 3.6.2.2

An excitatory cholinergic synapse (Nervous coordination)
Definitions
  • Excitatory postsynaptic potential (EPSP): a graded depolarisation of the postsynaptic membrane, produced by neurotransmitter binding, that makes a subsequent action potential more likely if it reaches threshold at the trigger region.
Key results
  • Synaptic transmission sequence (excitatory cholinergic synapse): action potential arrives at the presynaptic terminal → depolarisation opens voltage-gated Ca²⁺ channels, Ca²⁺ enters → synaptic vesicles containing acetylcholine (ACh) fuse with the presynaptic membrane and release ACh by exocytosis → ACh diffuses across the synaptic cleft and binds postsynaptic ligand-gated cation channels → channels open, net Na⁺ entry produces a graded EPSP → ACh is hydrolysed by acetylcholinesterase (AChE) into choline and acetate → choline is recycled, taken back up presynaptically to synthesise more ACh.
Notes
  • Chemical transmission across a synapse is strictly unidirectional: only the presynaptic terminal has the vesicle-release machinery, and only the postsynaptic membrane has the relevant receptors — information can only flow one way across any individual synapse.
  • Removing neurotransmitter from the cleft (here, AChE hydrolysing ACh) is essential, not incidental — without it, the postsynaptic receptors would remain continuously stimulated, preventing the synapse from responding to any further, discrete signal.
  • An EPSP is graded (varies in size) exactly like a generator potential, and only triggers an action potential if the combined depolarisation at the trigger region (from one or more EPSPs) reaches threshold — a single EPSP alone is not automatically sufficient.

Summation and inhibition at synapses 3.6.2.2

Summation and inhibition (Nervous coordination)
Definitions
  • Spatial summation: sub-threshold EPSPs arriving simultaneously from several different presynaptic neurones add together at the same postsynaptic trigger region.
  • Temporal summation: sub-threshold EPSPs arriving in rapid succession from ONE presynaptic neurone add together before the first has decayed away.
Notes
  • Both forms of summation solve the same underlying problem — a single sub-threshold EPSP alone is not enough to trigger an action potential — but via different routes: spatial summation combines input across space (multiple synapses), temporal summation combines input across time (repeated firing at one synapse).
  • Inhibitory synapses (via K⁺ efflux or increased Cl⁻ conductance) reduce the postsynaptic membrane's chance of firing, either by hyperpolarising it further from threshold or by 'shunting' (short-circuiting) excitatory current that would otherwise contribute to depolarisation.
  • An inhibitory postsynaptic potential (IPSP) arriving at the same time as excitatory EPSPs works directly against summation, making threshold correspondingly harder to reach — the trigger region's ultimate response reflects the net balance of all simultaneous excitatory and inhibitory input, not any one input considered alone.

Worked examples

Worked example 3.6.2 · 4 marks

Neurone P is unmyelinated with an axon diameter of 2 μm.

Neurone Q is myelinated with an axon diameter of 12 μm.

State, with reasoning, which neurone would be expected to conduct action potentials faster, referring to two separate structural factors.

Show worked solution

Neurone Q conducts faster.

Myelination means depolarisation only occurs at nodes of Ranvier, so the impulse 'jumps' between nodes (saltatory conduction) rather than propagating continuously.

Greater axon diameter offers less internal resistance to local currents, allowing them to spread further and faster before dying away.

Both factors independently favour Q.

Mark scheme · 4 marks

  • States neurone Q conducts faster 1 mark
  • Explains myelination enables saltatory conduction between nodes of Ranvier 1 mark
  • Explains greater diameter reduces internal resistance to local currents 1 mark
  • States both factors act independently, compounding the speed difference 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

Worked example 3.6.2 · 3 marks

A particular sensory neurone has an absolute refractory period of 2 milliseconds, during which a further action potential cannot be triggered under any circumstances.

Calculate the theoretical maximum frequency of action potentials this neurone could produce, expressed in impulses per second (Hz), and explain why the neurone's ACTUAL maximum firing frequency in practice would be somewhat lower than this calculated value.

Show worked solution

Theoretical maximum frequency:

The actual maximum would be lower because this calculation ignores the relative refractory period that follows, during which a further action potential requires a stronger-than-normal stimulus.

Mark scheme · 3 marks

  • Calculates 500 Hz as the theoretical maximum 1 mark
  • States the relative refractory period is not accounted for in this calculation 1 mark
  • Explains a stronger-than-normal stimulus is needed during the relative refractory period 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

3.6.3

Skeletal muscles

The neuromuscular junction 3.6.3

Neuromuscular junction (Nervous coordination)
Notes
  • The neuromuscular junction (NMJ) works by essentially the same mechanism as an excitatory cholinergic synapse (voltage-gated Ca²⁺ influx, ACh vesicle release, ligand-gated cation channels, AChE breakdown) — the key structural difference is that the postsynaptic membrane here is a specialised, deeply folded region of the muscle fibre's own membrane (the motor end plate), not another neurone.
  • At a healthy neuromuscular junction, one motor neurone impulse normally triggers exactly one muscle action potential — unlike many neurone-to-neurone synapses, where summation across multiple inputs is typically required to reach threshold.
  • Receptor blockade (a drug or toxin preventing ACh from binding its receptor) reduces depolarisation and so impairs muscle stimulation; AChE inhibition instead prolongs ACh's action at the synapse, since it cannot be broken down and removed normally — both disrupt the normal one-impulse-to-one-contraction relationship, but by opposite mechanisms (too little transmission vs too much/too prolonged transmission).

Antagonistic muscle pairs 3.6.3

Skeletal muscle as an effector (Skeletal muscle: structure, stimulation and contraction)
Definitions
  • Antagonistic muscle pair: two muscles arranged to pull in opposite directions across a joint, since a muscle can only actively pull (contract), never push.
Notes
  • At the elbow, the biceps contracts and shortens to flex the arm (raising the forearm) while the triceps relaxes; the triceps contracts and shortens to extend the arm (lowering the forearm) while the biceps relaxes — each movement direction requires one muscle of the pair to actively contract while its antagonist relaxes.
  • Muscles work against an effectively incompressible, rigid skeleton — tendons transmit a contracting muscle's tension directly to the bone it is attached to, converting muscle shortening into movement at the joint.
  • 'Contraction' specifically means tension production, not necessarily shortening — a muscle can contract isometrically (producing tension without changing length, e.g. holding a static position) as well as contracting and shortening to produce movement.

Muscle structure: from whole muscle to myofibril 3.6.3

From whole muscle to myofibrils (Skeletal muscle: structure, stimulation and contraction)
Notes
  • A whole muscle is organised hierarchically: a whole muscle is bundled into fascicles (bundles of muscle fibres), each fascicle contains many muscle fibres, and each muscle fibre contains many myofibrils.
  • A muscle fibre is one single, long, multinucleate cell (with nuclei arranged peripherally, just under the cell membrane), formed during development by the fusion of many individual precursor cells — genuinely unusual compared with most other body cells, which are mononucleate.
  • Each myofibril itself contains a series of repeating sarcomeres arranged end to end — the alignment of sarcomeres across adjacent myofibrils is what gives skeletal muscle its characteristic banded (striated) appearance under the microscope.

The sliding filament model 3.6.3

The sliding-filament mechanism (Skeletal muscle: structure, stimulation and contraction)
Definitions
  • Sliding filament model: contraction occurs as thin (actin) filaments slide past thick (myosin) filaments, shortening each sarcomere, without either filament itself changing length — the shortening comes entirely from increased overlap between the two filament types.
Key results
  • During shortening: the Z lines at each end of the sarcomere move closer together, filament overlap increases, the A band (myosin's own length) stays the same, the I bands (actin-only regions) become narrower, and the H zone (myosin-only region) may disappear entirely if overlap becomes great enough.
Notes
  • The A band staying the same length throughout contraction is direct, central evidence for the model: since the A band corresponds to the full length of the myosin filaments themselves, its constancy shows the filaments are not shortening — only their degree of overlap is changing.
  • A sarcomere is defined as extending from one Z line to the next; the I band is shared between two adjacent sarcomeres, each contributing half of it, which is worth remembering when interpreting a labelled diagram of a single sarcomere in isolation.
  • Neither filament type itself becomes shorter at any point in this process — the entire mechanism is a sliding motion, driven by many myosin heads cycling repeatedly (the cross-bridge cycle, covered next).

Excitation-contraction coupling 3.6.3

From nerve impulse to exposed binding sites (Skeletal muscle: structure, stimulation and contraction)
Notes
  • A muscle action potential, once triggered at the neuromuscular junction, spreads across the sarcolemma (muscle cell membrane) and down T-tubules that penetrate into the muscle fibre's interior, allowing depolarisation to reach deep within the cell almost instantly rather than relying on diffusion alone.
  • T-tubule depolarisation activates Ca²⁺ release channels on the sarcoplasmic reticulum (SR, an internal calcium-storing membrane system), releasing Ca²⁺ into the sarcoplasm.
  • At low sarcoplasmic Ca²⁺, tropomyosin covers the myosin-binding sites on actin, physically blocking cross-bridge formation. At raised sarcoplasmic Ca²⁺, Ca²⁺ binds troponin, causing tropomyosin to move away and expose the myosin-binding sites — this is the direct molecular switch that turns contraction on and off.
  • Relaxation reverses this: Ca²⁺ is actively pumped back into the SR (against its concentration gradient, requiring ATP), sarcoplasmic Ca²⁺ falls, Ca²⁺ dissociates from troponin, and tropomyosin re-covers the binding sites — relaxation is therefore itself an active, ATP-requiring process, not merely the passive absence of stimulation.

The actin-myosin cross-bridge cycle 3.6.3

The actin–myosin cross-bridge cycle (Skeletal muscle: structure, stimulation and contraction)
Key results
  • Cross-bridge cycle, per myosin head: (1) ATP binds the myosin head, detaching it from actin → (2) ATP is hydrolysed to ADP + Pi, re-cocking the myosin head → (3) the cocked head binds a new site on actin, forming a cross-bridge → (4) the power stroke: Pi, then ADP, are released, and the head pivots, pulling the actin filament toward the sarcomere's M line → cycle repeats, provided Ca²⁺ continues to expose binding sites and ATP remains available.
Notes
  • ATP has two genuinely distinct roles in this cycle, easily conflated: ATP BINDING detaches the myosin head from actin (step 1), while ATP HYDROLYSIS afterward re-cocks the head, storing the energy the following power stroke will release (step 2) — binding and hydrolysis are separate events with separate mechanical consequences.
  • Without ATP, myosin heads cannot detach from actin at all once bound — this is exactly why muscle tissue stiffens irreversibly (rigor mortis) once ATP production stops after death: existing cross-bridges become permanently locked in place.
  • Many myosin heads along a thick filament cycle repeatedly and asynchronously (not all in unison) — at any instant some heads are attached and pulling while others are detaching or re-cocking, producing smooth, continuous filament sliding rather than a jerky, all-at-once motion.

ATP supply for muscle contraction 3.6.3

ATP and phosphocreatine (Skeletal muscle: structure, stimulation and contraction)
Notes
  • ATP is needed for at least three distinct purposes in a contracting muscle fibre: detaching and re-cocking myosin heads in the cross-bridge cycle, actively pumping Ca²⁺ back into the sarcoplasmic reticulum during relaxation, and (indirectly) maintaining the ion gradients the muscle fibre relies on more generally.
  • Phosphocreatine provides a very rapid, short-term route to ATP regeneration: creatine kinase transfers a phosphate group directly from phosphocreatine to ADP, forming ATP and creatine — substrate-level phosphorylation, with no need for the multi-step pathways of aerobic or even anaerobic respiration.
  • Phosphocreatine buffers sudden, intense demand for ATP faster than aerobic respiration or glycolysis can respond, but its store is limited and is itself replenished (using ATP from respiration) during subsequent recovery — energy systems overlap in time rather than switching on and off sequentially, with phosphocreatine dominant in the first seconds of intense effort and respiration sustaining ATP supply thereafter.

Slow and fast skeletal muscle fibres 3.6.3

Slow- and fast-twitch fibres (Skeletal muscle: structure, stimulation and contraction)
Key results
  • Slow-twitch (oxidative) fibres: many mitochondria, dense capillary supply, more myoglobin, smaller fibre diameter — slower, fatigue-resistant contraction, relying mainly on aerobic ATP production; common in postural muscles (e.g. soleus).
  • Fast-twitch (glycolytic) fibres: fewer mitochondria, less dense capillary supply, less myoglobin, larger fibre diameter, large glycogen stores — rapid, forceful contraction that fatigues sooner, relying more on anaerobic glycolysis; common in limb muscles used for powerful movement (e.g. triceps).
Notes
  • Every structural difference between the two fibre types (mitochondria count, capillary density, myoglobin content, diameter) serves the same underlying functional trade-off: slow fibres are built to sustain aerobic ATP production for endurance, fast fibres are built to generate rapid, powerful contraction at the cost of quicker fatigue.
  • Most real muscles contain a mixture of both fibre types (plus fast-oxidative fibres, an intermediate type), with the exact proportions varying between different muscles and between individuals — 'slow-twitch muscle' and 'fast-twitch muscle' describe a fibre's dominant properties within a muscle, not a strict either/or classification applying to a whole muscle uniformly.

Worked examples

Worked example 3.6.3 · 5 marks

During skeletal muscle contraction, place the following events in the correct sequence, and briefly explain the role of each:

(i) myosin heads bind to actin, forming cross-bridges; (ii) calcium ions bind to troponin, causing tropomyosin to move and expose the actin binding sites; (iii) an action potential arrives at the neuromuscular junction and depolarises the sarcolemma; (iv) ATP binds to myosin heads, causing them to detach from actin;

(v) calcium ions are released from the sarcoplasmic reticulum.

Show worked solution

Correct sequence: (iii) →

(v) → (ii) →

(i) → (iv).

Depolarisation at the neuromuscular junction spreads via T-tubules to the sarcoplasmic reticulum, releasing Ca²⁺; Ca²⁺ binds troponin, moving tropomyosin to expose binding sites; myosin heads bind actin, forming cross-bridges and performing the power stroke; ATP then binds myosin, causing detachment.

Mark scheme · 5 marks

  • States the correct order: (iii), (v), (ii), (i), (iv) 1 mark
  • Explains depolarisation spreads via T-tubules to the sarcoplasmic reticulum 1 mark
  • Explains Ca²⁺ binding troponin moves tropomyosin, exposing binding sites 1 mark
  • Explains myosin heads bind actin and perform the power stroke 1 mark
  • Explains ATP binding causes myosin to detach from actin 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

Worked example 3.6.3 · 4 marks

A sprinter's leg muscle relies heavily on the immediate hydrolysis of phosphocreatine to regenerate ATP during the first few seconds of a sprint.

Explain the role of phosphocreatine in this context, and explain why this system alone cannot sustain muscle contraction for more than a few seconds.

Show worked solution

Phosphocreatine transfers a phosphate group directly and rapidly to ADP, regenerating ATP almost instantaneously, before respiration can increase its rate to meet sudden demand.

This system cannot sustain contraction long because the store of phosphocreatine in muscle cells is very small, and can only be replenished once demand for ATP falls again.

Mark scheme · 4 marks

  • States phosphocreatine transfers a phosphate group directly to ADP, regenerating ATP 1 mark
  • States this is faster than respiration can respond to sudden demand 1 mark
  • States the phosphocreatine store is very small 1 mark
  • States it can only be replenished once ATP demand falls 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

Worked example 3.6.3 · 4 marks

Muscle biopsies from two athletes are compared.

Athlete X's sample is dominated by slow-twitch (type I) fibres; athlete Y's sample is dominated by fast-twitch (type II) fibres.

State and explain which athlete is more likely to excel at long-distance marathon running, and which is more likely to excel at 100 m sprinting, referring to specific structural or metabolic properties of each fibre type.

Show worked solution

Athlete X excels at marathon running: slow-twitch fibres have many mitochondria, a rich blood supply and high myoglobin, suited to sustained aerobic effort.

Athlete Y excels at sprinting: fast-twitch fibres are larger, have fewer mitochondria, and rely on anaerobic glycolysis for fast but short-lived ATP supply.

Mark scheme · 4 marks

  • States athlete X (slow-twitch) suits marathon running 1 mark
  • States slow-twitch fibres have many mitochondria, rich blood supply and high myoglobin 1 mark
  • States athlete Y (fast-twitch) suits sprinting 1 mark
  • States fast-twitch fibres rely on anaerobic glycolysis for fast, short-lived ATP 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

3.6.4

Homeostasis

Principles of homeostasis and negative feedback 3.6.4.1

Homeostasis and negative feedback (Homeostasis: glucose regulation and osmoregulation)
Definitions
  • Homeostasis: maintenance of a stable internal environment within restricted limits, chiefly through negative feedback — a receptor detects a deviation from the normal range, a coordinator triggers effectors that counteract it, and the corrective response subsides once the variable returns toward normal.
Key results
  • Above the normal range: receptors and coordinator trigger a response that lowers the variable, moving it back toward the normal range. Below the normal range: receptors and coordinator trigger a response that raises the variable, again moving it back toward the normal range — in both cases, corrective activity subsides once the normal range is restored.
Notes
  • Core temperature, pH, blood glucose and water potential are all held within restricted limits because doing so provides suitable, stable conditions for enzyme activity, stable respiratory substrate availability, and stable cell volume — homeostasis is not an end in itself, but a precondition for normal cell and tissue function.
  • Because a corrective response is only triggered once a deviation has already been detected, and neither detection nor correction is instantaneous, homeostasis maintains a narrow controlled range around a set point rather than a genuinely constant, unchanging value — dynamic regulation, not elimination of variation altogether.
  • Positive feedback (amplifying rather than correcting a deviation, e.g. part of the process of childbirth) is comparatively rare in physiology, since an unchecked amplifying loop is generally harmful — where it does occur, it is normally self-limiting for a separate reason (e.g. running out of substrate, or being physically confined), reaching a definite endpoint rather than spreading uncontrolled.

Control of blood glucose concentration 3.6.4.2

Control of blood glucose (Homeostasis: glucose regulation and osmoregulation)
Definitions
  • Glycogenesis: glucose → glycogen (lowers blood glucose). Glycogenolysis: glycogen → glucose (raises blood glucose). Gluconeogenesis: production of new glucose from non-carbohydrate sources, a response to a prolonged glucose deficit.
Key results
  • Rising blood glucose: pancreatic islet β cells secrete insulin → muscle and adipose tissue take up more glucose (facilitated diffusion, via more GLUT4 transporters), liver and muscle carry out glycogenesis → blood glucose falls.
  • Falling blood glucose: pancreatic islet α cells secrete glucagon → liver carries out glycogenolysis, and gluconeogenesis if the deficit persists → blood glucose rises.
  • Type 1 diabetes: autoimmune destruction of β cells, little or no insulin produced — controlled with insulin therapy (by injection, since oral insulin would be digested) and diet management. Type 2 diabetes: insulin resistance combined with inadequate insulin secretion — managed with diet, physical activity and medicines, sometimes progressing to insulin; risk reflects genetic susceptibility, adiposity, physical activity and other environmental factors.
Method
  1. Finding the glucose concentration of an unknown sample (e.g. a urine sample) by colorimetric calibration curve: prepare a dilution series of glucose solution of known concentrations → react each with Benedict's reagent under identical, fixed conditions (same volume, same heating time and temperature) → measure the colour produced using a colorimeter, recording absorbance (or % transmission) for each known concentration → plot a calibration curve of colorimeter reading against known glucose concentration → treat the unknown sample identically and measure its colorimeter reading → read its glucose concentration from the calibration curve.
  2. This is the same core dilution-series-plus-colorimetric-calibration-curve technique used to find the water potential of plant tissue (see Osmosis and active transport) — only the reagent (Benedict's here, rather than simply weighing) and what is being measured differ; the underlying logic of converting an indirect, easily measured signal into a concentration via a curve built from known standards is identical.
Notes
  • This is a classic negative feedback system: as blood glucose returns toward the normal range, the original stimulus for hormone release (the deviation itself) diminishes, so insulin or glucagon secretion falls back toward baseline.
  • Measuring insulin concentration alongside glucose concentration is specifically what distinguishes type 1 from type 2 diabetes clinically — low/absent insulin points to type 1, while normal-or-elevated insulin alongside high glucose points to type 2 (insulin resistance, not insulin deficiency).

Hormone action: insulin and the second messenger model 3.6.4.2

Hormones act through specific cell-surface receptors (Homeostasis: glucose regulation and osmoregulation)
Key results
  • Insulin (muscle and adipose cells): binds a cell-surface receptor → promotes insertion of more GLUT4 glucose transporters into the membrane (more glucose uptake by facilitated diffusion) and activates enzymes for glycogen synthesis.
  • Glucagon or adrenaline (liver cell, second messenger model): hormone (first messenger) binds a cell-surface receptor → activates a G protein → activates adenylate cyclase → converts ATP to cyclic AMP (cAMP, the second messenger) → cAMP activates protein kinase → triggers an enzyme cascade leading to glycogenolysis (glycogen → glucose, released into the blood).
Notes
  • Glucagon (like many hormones) cannot cross the liver cell membrane directly, since it is not lipid-soluble — the second messenger model exists specifically to relay its signal into the cell via a cell-surface receptor, without the hormone itself ever entering.
  • Because each stage of the cascade is catalytic (one activated enzyme molecule can activate many downstream target molecules) rather than a one-to-one relay, the original signal is substantially amplified — a comparatively small number of glucagon molecules binding receptors can ultimately activate a much larger number of glycogen phosphorylase molecules.
  • This second-messenger amplification principle is a general mechanism, not a one-off fact specific to glucagon — it recurs wherever a hormone that cannot itself enter its target cell needs to produce a large, rapid intracellular effect.
  • Insulin and glucagon act via genuinely different mechanisms on different cell types (insulin promoting transporter insertion in muscle/adipose cells; glucagon triggering a second-messenger cascade in liver cells) — both regulate blood glucose, but should not be treated as mirror-image versions of the same mechanism.

The nephron: filtration and selective reabsorption 3.6.4.3

The nephron: filtration and selective reabsorption (Homeostasis: glucose regulation and osmoregulation)
Key results
  • Glomerular (ultra)filtration: blood enters the glomerulus at high hydrostatic pressure → water and small solutes (glucose, amino acids, ions, urea) pass through the fenestrated capillary endothelium, basement membrane and podocyte filtration slits into the Bowman's capsule (capsular space) — blood cells and most plasma proteins (too large) are retained in the blood.
  • Selective reabsorption (proximal convoluted tubule, PCT): Na⁺ is actively pumped out of the tubule cell (via a basal Na⁺/K⁺ pump, using ATP), creating a gradient that drives Na⁺-coupled cotransport of glucose from the tubule fluid into the cell across the microvilli-covered apical membrane → glucose then leaves the cell into the blood by facilitated diffusion → water follows the reabsorbed solutes by osmosis.
Notes
  • High capillary hydrostatic pressure in the glomerulus (created by the afferent arteriole being wider than the efferent arteriole) is what actually drives filtration — the same fundamental process as capillary filtration into tissue fluid elsewhere in the body, just occurring at a much higher rate and pressure here.
  • Podocyte filtration slits are the final, finest barrier determining exactly what can leave the blood at the glomerulus — their small size, combined with the basement membrane, is what excludes blood cells and most plasma proteins while still allowing water and small solutes through freely.
  • Under normal conditions, virtually all filtered glucose is recovered by selective reabsorption in the PCT — glucose appearing in urine (glycosuria) indicates the filtered amount has exceeded the tubule's reabsorption capacity, as happens with the elevated blood glucose of uncontrolled diabetes.

The loop of Henle and the medullary gradient 3.6.4.3

The loop of Henle establishes a medullary gradient (Homeostasis: glucose regulation and osmoregulation)
Notes
  • The loop of Henle establishes a water-potential gradient in the medulla that becomes progressively more negative with depth, via countercurrent flow: the thick ascending limb actively pumps NaCl out into the surrounding interstitium (using ATP) while itself remaining essentially impermeable to water, so water cannot simply follow it straight back out; the descending limb, by contrast, is permeable to water (but does not itself pump ions), so water leaves it by osmosis into the increasingly salty surrounding tissue.
  • Because the two limbs run in opposite directions immediately alongside each other, this countercurrent arrangement reinforces the gradient repeatedly along the loop's length, building a far steeper medullary gradient than a simple, non-countercurrent single-pass system could achieve.
  • Urea recycling also contributes to the medullary gradient, alongside the active NaCl pumping in the ascending limb — the gradient's full magnitude depends on both solutes, not sodium chloride movement alone.
  • This entire gradient is built in ADVANCE of any water actually being reabsorbed from the collecting duct — the loop of Henle does the underlying work of creating a very concentrated medullary environment, which the collecting duct (under ADH control, covered next) can then exploit as needed.
  • A longer loop of Henle (as in desert-adapted mammals such as the kangaroo rat) builds a steeper medullary gradient, letting the animal produce much more concentrated urine and conserve far more water than a species with a proportionally shorter loop.

ADH and control of blood water potential 3.6.4.3

ADH controls blood water potential (Homeostasis: glucose regulation and osmoregulation)
Definitions
  • Antidiuretic hormone (ADH): made in the hypothalamus and released into the blood from the posterior pituitary, ADH increases the permeability of the collecting duct to water by increasing the number of aquaporins inserted into its lumen-facing (apical) membrane.
Key results
  • Falling blood water potential (e.g. after water loss) → hypothalamic osmoreceptors detect the change → posterior pituitary releases more ADH → more aquaporins inserted into the late DCT and collecting duct membranes → more water reabsorbed (leaving the duct lumen by osmosis, into the concentrated medullary interstitium, and returning to the blood via capillaries) → a smaller volume of more concentrated urine — and blood water potential rises back toward normal.
  • Rising blood water potential reverses every step of this chain: less ADH → fewer apical aquaporins → less water reabsorption → a larger volume of more dilute urine.
Notes
  • Because proximal convoluted tubule reabsorption is largely fixed and unregulated, it is specifically this adjustable, ADH-controlled step at the DCT and collecting duct that gives the kidney its actual moment-to-moment control over blood water potential — disproportionate to its comparatively small share of the total water reabsorbed along the whole nephron.
  • The loop of Henle's pre-built medullary gradient (covered in the previous section) is what the collecting duct actually exploits: ADH simply determines how MUCH of that pre-existing gradient the duct is allowed to use at any given moment, by controlling aquaporin insertion — it does not itself create the gradient.
  • As blood water potential recovers toward normal, the original stimulus for ADH release diminishes and ADH secretion decreases — another direct example of negative feedback, exactly analogous to the pattern already established for blood glucose control.

Worked examples

Worked example 3.6.4 · 4 marks

One glucagon molecule binding to a liver cell receptor activates one molecule of adenylate cyclase, which produces 100 molecules of cAMP per second while active.

Each cAMP molecule activates one molecule of protein kinase A, and each activated protein kinase A molecule activates 20 molecules of the next enzyme in the cascade over the same period.

Calculate the overall amplification factor from one glucagon molecule to the number of next-stage enzyme molecules activated in one second, and explain what this demonstrates about the second messenger model.

Show worked solution

Amplification:

One glucagon molecule results in 2000 next-stage enzyme molecules activated within one second.

This demonstrates the second messenger model amplifies a signal at every catalytic step, so a small hormone concentration change produces a much larger intracellular response.

Mark scheme · 4 marks

  • Calculates amplification = 2000 1 mark
  • States each stage of the cascade is itself catalytic 1 mark
  • Explains this multiplies the effect of a single hormone-receptor binding event at every step 1 mark
  • Concludes a small hormone concentration change produces a much larger metabolic response 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

Worked example 3.6.4 · 5 marks

A patient produces 1.5 dm³ of urine per day when well hydrated.

After 12 hours without water, ADH release increases substantially and urine output falls to 0.4 dm³ per day (measured as an instantaneous rate over that period).

Explain, in terms of the nephron's structure and function, how increased ADH release brings about this fall in urine output.

Show worked solution

Increased ADH acts on the distal convoluted tubule and collecting duct, increasing the number of aquaporins in their cell-surface membranes.

More water is reabsorbed by osmosis down the water potential gradient maintained by the loop of Henle in the medulla.

Greater reabsorption means less water remains in the tubule fluid to be excreted, producing a smaller volume of more concentrated urine.

Mark scheme · 5 marks

  • States ADH acts on the distal convoluted tubule and collecting duct 1 mark
  • States ADH increases the number of aquaporins in the cell-surface membrane 1 mark
  • States more water is reabsorbed by osmosis, down the gradient maintained by the loop of Henle 1 mark
  • Explains less water remains in tubule fluid, giving smaller volume, more concentrated urine 1 mark
  • Links this to the body conserving water to restore blood water potential 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.

Worked example 3.6.4 · 5 marks

A patient with severe kidney damage is found to have glucose present in their urine, despite having a normal blood glucose concentration.

Explain, with reference to the specific structures involved, what this observation suggests has gone wrong in the nephron, distinguishing this from the separate cause of glucose in urine seen in uncontrolled diabetes.

Show worked solution

Glucose normally enters the filtrate at the glomerulus but is fully reabsorbed at the proximal convoluted tubule by co-transport with sodium.

Glucose in urine with normal blood glucose suggests a fault in this reabsorption mechanism itself.

In uncontrolled diabetes, by contrast, reabsorption is not faulty, but blood glucose is so high the filtrate glucose exceeds reabsorption capacity.

Mark scheme · 5 marks

  • States glucose is normally fully reabsorbed at the proximal convoluted tubule by co-transport 1 mark
  • States glucose in urine with normal blood glucose suggests a faulty reabsorption mechanism 1 mark
  • States in diabetes, reabsorption is not faulty 1 mark
  • Explains in diabetes, filtrate glucose exceeds reabsorption capacity due to high blood glucose 1 mark
  • Distinguishes the two causes as a faulty mechanism versus an overwhelmed normal one 1 mark

Do not count matching words alone — ask whether your answer actually makes the same claim.