@ 4plicationsà Secretion and reabsorption of acetglcholine bg

neurons at sunapses.à Blocking of sgnaptic transmission at

cholinergic sUnapses ¡n insects bg bindingof neonicotinoid pesticides to acetglcholinerecePtors.

@ smnsÐ Analgsis of oscilloscoPe traces showing resting

potentials and action potentials.

@ nature of sc¡enceÐ Cooperation and collaboration between groups

of scientists: biologists are contribut¡ngtoresearch ¡nto memorg and learning.

Understandingà Neurons transmit electrical impulses.

Ð The mgelination of nerve fibres allows forsaltatorg conduction.

à Neurons pump sodium and potassium ionsacross their membranes to generate a restingpotential.

+ An action potential consists of depolarizationand repolarization of the neuron.

-) Nerve impulses are action potentialspropagated alongthe axons of neurons.

Ð Propagation of nerve impulses is the result oflocal currents that cause each successive partof the axon to reach the threshold potential.

à Sgnapses are junctions between neurons and

between neurons and recePtor or effeclor cells.

) When pre-sgnaPtic neurons are depolarizedtheg release a neurotransmitter into thesunapse.

Ð A nerve impulse is onlg initiated if the thresholdpotentlal is reached

NeuronsNeurons transmit electrical impulses.Two systems of the body are used for internal communication: theendocrine system and the nervous system. The endocrine systemconsists of glands that release hormones. The nervous systemconsists of nerve cells called neurons. There are about 85 billionneurons in the human nervous system. Neurons help with internalcommunication by transmitting nerve impulses. A nerve impulse isan electrical signal.

Neurons have a cell body with cytoplasm and a nucleus but theyalso have narrow outgrowths called nerve flbres along which nerveimpulses travel.

o Dendrites are short branched nerve fibres, for examples those usedto transmit impulses between neulons in one part of the brain orspinal cord.

o Axons aIe very elongated nerve fibres, for example those that transmitimpulses from the tips o1 the toes or the flngers to the spinal cord.

HUMAN PHYSIOLOGY

cell bodu

ax0n

dendrites skeletal muscle IeffectorJ

a Figure 1 Neuron with dendrites that transmit impulses to the cell bodg and an axon that transmits impulses a considerabledistance to muscle f ibres

À Figure 2 Nerve fibres Iaxons) transmittingelectrical impulses to and from the centralnervous sustem are grouped into bundles

mgelin nucleus of node ofsheath Schwann cell Ranvier

------> ..-----> ----->

a Figure 3 Detait o?il,r.,,nr..d nervefibre showing the gaps between adjacentSchwann cells Inodes of RanvierJ

Mgelinated nerue fibresThe mgelination of nerve fibres allows for saltatorgconduct¡on.The basic structure of a nerve fibre along which a nerve impulse istransmitted is very simple: the flbre is cylindrical in shape, with a plasmamembrane enclosing a narrow region of cytoplasm. The diameter inmost cases is about I pm, though some nerve fibres are wider than this.A nerve flbre with this simple structure conducts nerve impulses at aspeed of about I metre per second.some nerve fibres are coated along most of their length by a materialcalled myelin. It consists of many layers of phospholipid bilayer. Specialcells called schwann cells deposit the myelin by growing round andround the nerve flbre. Each time they grow around the nerve flbre adouble layer of phospholipid bilayer is deposited. There may be 20 ormore layers when the Schwann cell stops growing.There is a gap between the myelin deposited by adjacent schwann cells.The gap is called a node of Ranvier. In myelinated nerve fibres the nerveimpulse can jump from one node of Ranvier to the next. This is calledsaltatory conduction. It is much quicker than continuous transmissionalong a nerve flbre so myelinated nerve fibres transmit nerve impulsesmuch more rapidly than unmyelinated nerve flbres. The speed can be asmuch as 100 metres per second.

Ä Figure 4 Transverse section of axon showing the mgelin sheath formed bg the Schwanncell's membrane wrapped round the axon manU times (red]

Resting potent¡alsNeurons pump sodium andpotassium ions across theirmembranes to generate a restingpotential.A neuron that is not transmitting a signalhas a potential difference or voltage across itsmembrane that is called the resting potential'This potential is due to an imbalance of positiveand negative charges across the membrane.

o Sodium-potassium pumps transfersodium (Na+) and potassium (I(+) ionsacross the membrane. Na+ ions are pumpedout and I(+ ions are pumPed in. Thenumbers of ions pumped is unequal - whenthree Na+ ions are pumped out, only twoI(+ ions are pumped in, creatingconcentration gradients for both ions'

o Also the membrane is about 50 times morepermeable to I(+ ions than Na+ ions, soI(+ ions leak back across the membranefaster than Na+ ions. As a result, theNa+ concentration gradient across themembrane is steeper than the I(+ gradient,creating a charge imbalance.

fluid outside neuron

protein @cUloplasm

A Figure 5 The resting potential is generated bg the sodium-potassium pump

@

@

a In addition to this, there are proteins inside the nerve fibre that arenegatively charged (organic anions), which increases the chargeimbalance.

These factors togethel give the neuron a resting membrane potential ofabout -70 mV

Action potent¡alsAn action potent¡al consists of depolarization andrepolar¡zation of the neuron.An action potential is a rapid change in membrane potential, consistingof two phases:

o depolarization - a change from negative to positive

o repolarization - a change back from positive to negative.

Depolarization is due to the opening of sodium channels in themembrane, allowing Na+ions to diffuse into the neuron down theconcentration gradient. The entry of Na+ ions reverses the chargeimbalance across the membrane, so the inside is positive relative tothe outside. This raises the membrane potential to a positive value ofabout l-30 mV.

HUMAN PHYSIOLOGY

fluid outslde neuron

prote¡n

cAtoplasm

A Figure 6 Neuron depolarizing

----) impulse movement+++++++++

@@fluid outside neuron

@

protein

catoplasm

A Figure Z Neuron repolarizing

Repolarization happens rapidly after depolarization and is dueto the closing of the sodium channels and opening of potassiumchannels in the membrane. This allows potassium ions to diffuseout of the neuron, down their concentration gradient, which makesthe inside of the cell negative again relative to the outside. Thepotassium channels remain open until the membrane has fallen toa potential close to -70 mv. The diffusion of potassium repolarizesthe neuron, but it does not restore the resting potential as theconcentration gradients of sodium and potassium ions have not yetbeen re-established. This takes a few milliseconds and the neuron canthen transmit another nerve impulse.

Propagation of action potentialsNerve impulses are act¡on potent¡als propagated alongthe axons of neurons.A nerve impulse is an action potential that starts at one end of a neuronand is then propagated along the axon to the other end of the neuron.The propagation of the action potential happens because the ionmovements that depolarize one part of the neuron trigger depolarizationin the neighbouring part of the neuron.Nerve impulses always move in one direction along neurons in humansand other vertebrates, This is because an impulse can only be initiated atone terminal of a neuron and can only be passed on to other neurons or

Acell membranecgtoplasm

^l Figure 8 Action potentials are propagatedalong axons

6.5 NEURONS AND SYNAPSES

different cell types at the other terminal. Also, there is a refractive period

after a depolarization that prevents propagation of an action potentialbackwards along an axon.

Local currentsPropagation of nerve impulses is the result of local

currents that cause each success¡ve part of the axon to

reach the threshold Potential.

inside and outside the axon.

Opening of the sodium channels causes depolarization'

a wave of dePolarization and thengated along the axon at a rale of between onemetres Per second'

,q{.iltvt'{ U

Neurons in a sea anemoneand an anemonefish

Anemonefish have a nervoussgstem similarto ours, with acentral nervous sustem andneurons that transmit nerveimpulses in one directiononlg. Sea anemones haveno central nervous sgstem.Their neurons form a simPlenetwork and will transmitimpulses in either directionalong their nerve f ibres' Theg

both protect each other frompredators more effectivel g

than theg can themselves.Explain how theg do this.

i* Figure 9 Anemonef ish amongthe tentacles of a sea anemone

impulse movement

qç

+Na

outside

insidemembrane

&a+ ¿¡6115\on

part that has iust dePolarized

Iaction potential]

part that has not get dePolarized

Iresting PotentialJ

A Figure 10 Local currents

HUMAN PHYSIOLOGY

-+3 sOcooõ= 0

-c.OOcLoØË3 suÀL ooz0

action potential peak

oothreshold potenrial

undershoot resting potential

@ mrlgsing oscilloscope tracesAnalgsis of oscilloscope traces showing restingpotentials and action potentials.

1,234567time/ms

0

Istimulus

À Figure 11 Changes in membrane polaritgduring an action potential

Data-based questions: Analgsing an oscilloscoThe oscilloscope trace in figure l2 was taken froma digital oscilloscope. It shows an action potentialin a mouse hippocampal pyramidal neuron thathappened after the neuron was stimulated with apulse of current.

Pe traceI State the resting potential of the mouse

hippocampal pyramidal neuron.2 Deduce with a reason the threshold

potential needed to open voltage_gatedsodium channels in this neuron.

3 Estimate the time taken for thedepolarization, and the repolarization. 12)

4 Predict the time taken from the end of thedepolarization for the resting potentialto be regained. pl

5 Discuss how many action potentialscould be stimulated per second in thisneuron. pl

ttl

l2

ss0€oúGõ0oco

!E -soE

resti potential

0 50time Ims]

100

T?F gure^ó Suggest a reason for the membrane

potential rising briefly at the end of therepolarization. tll

SgnapsesSgnapses are junctions between neurons and betweenneurons and receptor or effector cells.synapses are junctions between cells in the nervous system. In scnse organsthere are synapses between sensory receptor ceils and neurons. In boththe brain and spinal cord there are immense numbers of synapses betweenneurons. In muscles and glands there are synapses between neurons and

6.51{EUR0t'ls AN0

musclefibresorsecretolycells.Musclesandglandsaresometimescalledeffectors, because they eifect (carry out) a response to a stimulus'

Chemicals called neuïotransmitters are used to send signals across

synapses. This system is used at all synapses where the pre-synaptic

and post-synaptic cells are separatedby a fluid-fiIled gap' so electrical

impulses cannot pass across' ittit gup is called the synaptic cleft and is

only about 20 nm wide.

Sgnaptic transmissionWhen pre-sgnapt¡c neurons are depolarized theg release

e neurotransm¡tter into the sgnapse'Synaptic transmission occurs very rapidly as a result of these events:

o A netve impulse is propagated along the pre-synaptic neuronuntil it reaches the end of the neuron and the pre-synapticmembrane'

o Depolarization of the pre-synaptic membrane causes

calcium ions (Ca2+) to diffuse through channels in the

membrane into the neuron'

Influx of calcium causes vesicles containingneurotransmitter to move to the pre-synapticmembrane and fuse with it'Neurotransmitter is released into the synaptic cleft byexocytosis.

The neurotransmitter diffuses across the synapticcleft and binds to receptors on the post-synapticmembrane.The binding of the neurotransmitter to the receptorscauses adjacent sodium ion channels to open'

Sodium ions diffuse down their concentration gradientinto the post-synaptic neuron, causing the post-synaptic mer.tbrun" to reach the threshold potential'

An action potential is triggered in the post-synapticmembrane and is propagated on along the neuron'

The neurotransmitter is rapidly broken down andremoved from the synaptic cleft'

À Figure 13 Electron micrograph of a sgnapse'

False colour has been used to indicate the

pre-sgnaptic neuron Ipurple] with vesicles of

neurotransmitter Iblue) and the post-sgnaptlc

neuron Ipink]. The narrowness ofthe sgnaptic

cleft is visible

pre-sgnaPtic cell

Ca2+diffusesinto knob

n eu rotra n smitterectivates r 0rs

post-sgnaPtic cell

nerveimpulse

@

tsgnaptic knob

sgnaptic vesicles

BneurotransmilterIe.g. acetglcholin

a

I¡¡

pre-sunaptlcmembrane

sgnaptic cleft20nm approximatelg

aa

a

o

ion channel oPened

post-sgnaPticmembrane

A Figure 14 A nerve impulse is propagated across a sgnapse bg the

,.Lr.., diffusion and post-sgnaptic binding of neurotransmitter

Data-based questions: Parkinson's disease

Dopamine is one of the many neurotransmittersthat are used at synapses in the brain' InParkinson's disease, there is a loss of dopamine-secreting neurons, which causes slowness ininitiating movement, muscular rigidity andin many cases shaking. Figure I5 shows the

metabolic pathways involved in the lormationand breakdown of doPamine'

I Explain how symptoms of Parkinson's disease

ará reüeved by giving the following drugs:

a) L-DOPA tll

HUMAN PHYSIOLOGY

b) sclcgeline, which is an inhibitor ofmonoamine oxidase_B (MAO_B) ttlc) tolcapone, which is an inhibitorof catechol- O -methyl transferase(coMr) tlld) ropinirole, which is an agonist ofdopamine tlle) safinamide, which inhibits reuptakeof dopamine by pre-synapticneurons. Iil2 Discuss how a cure for parkinson,s disease

might in the future be developed by:a) srem cell therapy t3lb) gene therapy. L2l

tgrosine C00ro-Gc¡rCf Ho

L-DOPA 00Hc

CH

I F00D ] NH,H

cHrNH,

dopad eca rboxg I a se

COMT

IdopaminecH30

cH30

cH- H HO

HO

cH-cH- NH,

I ¡/A0-B

CH¡0

{

IH

aldehgdedehgdrogenase

cH- C00HcH-cooH g- Ho

HO

Ä Figure 15 The formation and breakdown of L_D0pA anddopamine. The enzgmes catalgsing each ste p are shown in red

AcetglcholineSecretion and reabsorption of acetgrcholine bg neuronsat sunapses.

@ neonicotinoidsBlocking of sgnaptic transmission at cholinergicsUnapses in insects bg binding of neonicotinoidpesticides to acetglcholine receptors.Neonicotinoids are synt to nicotine. Theybind to the acetylcholin synapses in thecentral nervous system terase does not

choline

acet gl group

A Figure 16 Acetglcholine

insecticides.

mammals than insects.

government agencies.

Threshold PotentialsA nerve impulse is onlg initiated if the thresholdpotential is reached.Nerve impulses follow an all-or-nothing principle. An action potential is only

initiated if the threshold potential is reached, because only at this potential

do voltage-gated sodium channels start to open' causing depolarization' The

op"rrirrg"otlome sodium channels and the inward diffusion of sodium ions

irrc."ases the membrane potential causing more sodium channels to open -there is a positive feedback effect. ff the threshold potential is reached there

will therefore always be a full depolarization'

At a synapse, the amount of neurotransmitter secreted lollowingdepolårizåtion of the pre-synaptic membrane may not be enough to cause

thã threshold potentiãl to be reached in the post-synaptic membrane'

Thepost-synapticmembranedoesnotthendepolarize.Thesodiumionsthat have entered the post-synaptic neuron are pumped out by sodium-potassiumpumpsandthepost-synapticmembranereturnstotherestingpotential.

A typical post-synaptic neuron in the brain or spinal cord has synapses

.roi¡.tr, with one but with manY pre-synaptic neurons' It may be

,r".érru.y for several of these to release neurotransmitter at the same

time for the threshold potential to be reached and a nerve impulse to

be initiated in the post:synaptic neuron' This type of mechanism can

beusedtoprocessinformationfromdifferentSoufcesinthebodytohelp in decision-making.

ActivitgResearch updates onneonicotinoids

There are currentlgintense research effortsto trv to discover whetherneonicotinoids are to blamefor collapses in honegbeecolonies, What are the mostrecent research findingsand do theg suggestthatthese insecticides shouldbe banned?

r Figure 17 Research hasshown that the neonicotinoidpesticide imidacloPrid reducesgrowth of bumblebee colonies

A Figure 18 Mang sgnapses are visible in thisscanning electron micrograph between the cellbodg ofone post-sunaptic neuron and a largenumber of different pre-sUnaptic neurons IblueJ

A Figure 19 Memorg and learning are functionsof the cerebrum-the folded upper part ofthe brain

@ nesearch into memorg and learningCooperation and collaboration between groups ofscientists: biologísts are contributing to iesearch intomemorg and learning.

o Professor Gero Miesenböck _ medicine and physiologyo Dr Martin Booth - engineering and optical microscopyo Dr I(orneel Hens - chemistry and biochemistryo Professor Scott Waddelt _ genetics, molecular biology and

neurobiology.