Level 5 — MasteryNervous System

Nervous System

75 minutes60 marksprintable — key stays hidden on paper

Difficulty: Level 5 — Mastery (cross-domain: biophysics + math + coding) Time limit: 75 minutes Total marks: 60

Instructions: Answer all three questions. Show full working. Use ...... notation for equations. Numerical answers to 3 significant figures unless stated otherwise. Physical constants: R=8.314 Jmol1K1R = 8.314\ \mathrm{J\,mol^{-1}K^{-1}}, F=96485 Cmol1F = 96485\ \mathrm{C\,mol^{-1}}, T=310 KT = 310\ \mathrm{K} (body temp) unless told otherwise.


Question 1 — Resting Potential: Nernst, Goldman & Ion Logic (22 marks)

A mammalian neuron at T=310 KT = 310\ \mathrm{K} has the following ion concentrations (mM):

Ion Inside Outside
K+\mathrm{K^+} 140 5
Na+\mathrm{Na^+} 15 145
Cl\mathrm{Cl^-} 10 110

(a) State the Nernst equation and explain physically why an equilibrium potential exists for a single permeant ion. (3)

(b) Calculate the Nernst (equilibrium) potential for K+\mathrm{K^+} and for Na+\mathrm{Na^+} in mV. (4)

(c) Using the Goldman–Hodgkin–Katz (GHK) equation with permeability ratios PK:PNa:PCl=1:0.04:0.45P_K : P_{Na} : P_{Cl} = 1 : 0.04 : 0.45, compute the resting membrane potential VmV_m. State the equation you use and take care with the Cl\mathrm{Cl^-} term. (6)

(d) The measured resting potential is about 70 mV-70\ \mathrm{mV}, yet VmV_m is not equal to EKE_K. Explain the two structural/functional features (one passive, one active) that account for this discrepancy and for the long-term maintenance of the gradients. (4)

(e) Explain quantitatively why doubling extracellular K+\mathrm{K^+} (5 → 10 mM) shifts EKE_K, and compute the new EKE_K. Comment on the clinical relevance to hyperkalemia. (5)


Question 2 — Action Potential & Saltatory Conduction: Modelling (22 marks)

(a) Sketch (labelled axes: mV vs ms) and describe the phases of an action potential: resting, depolarisation, repolarisation, hyperpolarisation. For each phase name the ion channel state responsible. (6)

(b) Explain the molecular basis of the absolute and relative refractory periods and why they enforce unidirectional propagation. (4)

(c) Conduction velocity in unmyelinated axons scales as vdv \propto \sqrt{d} (diameter), whereas in myelinated axons vdv \propto d (linear). A squid giant axon of diameter 500 μm500\ \mu\mathrm{m} conducts at 25 ms125\ \mathrm{m\,s^{-1}} (unmyelinated). A myelinated mammalian axon of diameter 20 μm20\ \mu\mathrm{m} conducts at 120 ms1120\ \mathrm{m\,s^{-1}}. (i) A reflex requires signal transfer over 1.0 m1.0\ \mathrm{m}. Compute the conduction time for each axon. (3) (ii) To match the myelinated axon's velocity with an unmyelinated axon of the same base scaling, what diameter would be required? Comment on biological feasibility. (4)

(d) Write pseudocode (or Python) for a simple integrate-and-fire neuron model that increments membrane potential by synaptic input each timestep, fires a spike when VVthresholdV \ge V_{threshold}, then resets. Include the refractory logic. (5)


Question 3 — Synapse, Reflex Arc & Autonomic Integration (16 marks)

(a) Describe the sequence of events in chemical synaptic transmission from action-potential arrival at the presynaptic terminal to postsynaptic response. Include the role of Ca2+\mathrm{Ca^{2+}}. (5)

(b) Draw and label the components of a monosynaptic reflex arc (e.g. knee-jerk). Explain why this reflex does not require the brain, and identify which neuron types (sensory/motor/interneuron) are present. (5)

(c) A person is startled. Compare the effects of sympathetic vs parasympathetic activation on: heart rate, pupil diameter, and gut motility. Name the dominant neurotransmitter released at the target organ for each division. (6)

Answer keyMark scheme & solutions

Question 1

(a) (3) Nernst equation: Eion=RTzFln[ion]out[ion]inE_{ion} = \dfrac{RT}{zF}\ln\dfrac{[\text{ion}]_{out}}{[\text{ion}]_{in}} (1). An equilibrium potential exists because ion movement is driven by two opposing forces — the chemical (concentration) gradient and the electrical gradient (1); at EionE_{ion} the electrical force exactly balances the diffusion force so net flux = 0 (1).

(b) (4) Use RTF=8.314×31096485=0.02671 V=26.71 mV\dfrac{RT}{F} = \dfrac{8.314\times310}{96485} = 0.02671\ \mathrm{V} = 26.71\ \mathrm{mV}; z=+1z=+1.

  • EK=26.71ln(5/140)=26.71×(3.332)=89.0 mVE_K = 26.71\ln(5/140) = 26.71\times(-3.332) = -89.0\ \mathrm{mV} (2)
  • ENa=26.71ln(145/15)=26.71×(2.269)=+60.6 mVE_{Na} = 26.71\ln(145/15) = 26.71\times(2.269) = +60.6\ \mathrm{mV} (2)

(c) (6) GHK: Vm=RTFlnPK[K]o+PNa[Na]o+PCl[Cl]iPK[K]i+PNa[Na]i+PCl[Cl]oV_m = \dfrac{RT}{F}\ln\dfrac{P_K[K]_o + P_{Na}[Na]_o + P_{Cl}[Cl]_i}{P_K[K]_i + P_{Na}[Na]_i + P_{Cl}[Cl]_o} (note Cl inverted because z=1z=-1) (2). Numerator: 1(5)+0.04(145)+0.45(10)=5+5.8+4.5=15.31(5) + 0.04(145) + 0.45(10) = 5 + 5.8 + 4.5 = 15.3 (1). Denominator: 1(140)+0.04(15)+0.45(110)=140+0.6+49.5=190.11(140) + 0.04(15) + 0.45(110) = 140 + 0.6 + 49.5 = 190.1 (1). Vm=26.71ln(15.3/190.1)=26.71×(2.521)=67.3 mVV_m = 26.71\ln(15.3/190.1) = 26.71\times(-2.521) = -67.3\ \mathrm{mV} (2).

(d) (4) Passive: the membrane is far more permeable to K+\mathrm{K^+} than Na+\mathrm{Na^+} at rest (leak K channels), so VmV_m sits near but not at EKE_K; the small Na+\mathrm{Na^+} leak pulls it positive of EKE_K (2). Active: the Na+/K+\mathrm{Na^+/K^+}-ATPase pumps 3 Na out / 2 K in per ATP, restoring gradients and contributing a small electrogenic hyperpolarising current, maintaining the resting state long-term (2).

(e) (5) EKE_K depends on the log of the ratio; doubling [K]o[K]_o changes ratio 5/140 → 10/140 (2). EKnew=26.71ln(10/140)=26.71×(2.639)=70.5 mVE_K^{new} = 26.71\ln(10/140) = 26.71\times(-2.639) = -70.5\ \mathrm{mV} (2). EKE_K becomes less negative (depolarised by ~18.5 mV), moving resting potential toward threshold → increased excitability; in hyperkalemia this causes cardiac arrhythmias / eventual inactivation of Na channels (1).


Question 2

(a) (6) — 1.5 marks per phase (½ description, ½ channel + ½ shape):

  • Resting 70-70 mV: voltage-gated Na/K closed, leak channels set potential.
  • Depolarisation: voltage-gated Na+\mathrm{Na^+} channels open, Na influx, rapid rise to ~+30 mV.
  • Repolarisation: Na channels inactivate; voltage-gated K+\mathrm{K^+} channels open, K efflux, potential falls.
  • Hyperpolarisation (undershoot): slow K channel closure overshoots below rest, then leak restores. Labelled sketch with mV/ms axes and threshold line (~55-55 mV).

(b) (4) Absolute refractory period: Na channels are inactivated (ball-and-chain), cannot reopen regardless of stimulus (2). Relative refractory period: K channels still open + some Na recovered → larger-than-normal stimulus needed (1). Because the region just fired is refractory, the AP can only propagate forward into un-refractory membrane → unidirectional (1).

(c)(i) (3) Unmyelinated: t=1.0/25=0.0400 s=40.0 mst = 1.0/25 = 0.0400\ \mathrm{s} = 40.0\ \mathrm{ms} (1.5). Myelinated: t=1.0/120=0.00833 s=8.33 mst = 1.0/120 = 0.00833\ \mathrm{s} = 8.33\ \mathrm{ms} (1.5).

(c)(ii) (4) vdv2/v1=d2/d1v \propto \sqrt d \Rightarrow v_2/v_1 = \sqrt{d_2/d_1}. 120/25=d2/500120/25 = \sqrt{d_2/500} (1) → (4.8)2=d2/500(4.8)^2 = d_2/500 (1) → d2=23.04×500=11520 μm11.5 mmd_2 = 23.04\times500 = 11520\ \mu\mathrm{m} \approx 11.5\ \mathrm{mm} (1). This is biologically infeasible — an 11.5 mm axon is enormous; myelination achieves high velocity with a 20 µm axon, a ~500× space saving (1).

(d) (5) — award for: increment (1), threshold test (1), spike+reset (1), refractory counter (1), loop structure (1).

def integrate_and_fire(inputs, V_thresh=-55, V_reset=-70, V_rest=-70, refrac=2):
    V = V_rest
    spikes = []
    ref_timer = 0
    for t, I in enumerate(inputs):
        if ref_timer > 0:          # refractory: ignore input
            ref_timer -= 1
            V = V_reset
            continue
        V += I                     # integrate synaptic input
        if V >= V_thresh:          # fire
            spikes.append(t)
            V = V_reset            # reset
            ref_timer = refrac     # enter refractory period
    return spikes

Question 3

(a) (5) — 1 mark each: AP reaches terminal → opens voltage-gated Ca2+\mathrm{Ca^{2+}} channels; Ca2+\mathrm{Ca^{2+}} influx triggers vesicle fusion with presynaptic membrane; neurotransmitter released by exocytosis into cleft; diffuses and binds receptors on postsynaptic membrane; opens ion channels → EPSP/IPSP; then neurotransmitter removed (reuptake/enzyme degradation).

(b) (5) Components (label any 5): receptor (muscle spindle) → sensory (afferent) neuron → dorsal root → spinal cord (integration centre) → motor (efferent) neuron → effector (muscle) (3). No brain required because integration occurs at the spinal cord synapse — faster, protective (1). Monosynaptic stretch reflex has sensory + motor neurons only (no interneuron); withdrawal reflexes add interneurons (1).

(c) (6) — 1 mark per correct cell:

Target Sympathetic Parasympathetic
Heart rate ↑ increase ↓ decrease
Pupil dilate (mydriasis) constrict (miosis)
Gut motility ↓ decrease ↑ increase

Target-organ neurotransmitter: sympathetic → noradrenaline (norepinephrine) at most targets; parasympathetic → acetylcholine (2 marks for the two transmitters).

[
  {"claim":"E_K approx -89.0 mV", "code":"RT_F=8.314*310/96485*1000; E_K=RT_F*log(Rational(5,140)); result = abs(float(E_K)-(-89.0))<0.5"},
  {"claim":"E_Na approx +60.6 mV", "code":"RT_F=8.314*310/96485*1000; E_Na=RT_F*log(Rational(145,15)); result = abs(float(E_Na)-60.6)<0.5"},
  {"claim":"GHK V_m approx -67.3 mV", "code":"RT_F=8.314*310/96485*1000; num=1*5+0.04*145+0.45*10; den=1*140+0.04*15+0.45*110; Vm=RT_F*log(num/den); result = abs(float(Vm)-(-67.3))<0.6"},
  {"claim":"New E_K with 10mM outside approx -70.5 mV", "code":"RT_F=8.314*310/96485*1000; E=RT_F*log(Rational(10,140)); result = abs(float(E)-(-70.5))<0.6"},
  {"claim":"Diameter for 120 m/s unmyelinated approx 11520 um", "code":"d=(120/25)**2*500; result = abs(d-11520)<50"}
]