3. Resting potentialResting potential
There is a potential
difference between the
inside and outside of as
membrane. The inside
is about -70 mv
relative to the outside.
Azam Basheer
4. Resting PotentialResting Potential
The resting potential is
caused by an uneven
distribution of ions
(electrically charged
molecules) of potassium
(K+) and sodium (Na+)
and chloride (Cl-).
This is caused by Na+/K+
ion pumps that move 3
Na+ ions out of the cell for
every 2 K+ ions it moves
in.
Therefore there are more
+ions outside the cell than
inside and the inside is
negatively charged with
respect to the outsideAzam Basheer
7. Action potentialAction potential
► Anything that alters the functioning of the ionAnything that alters the functioning of the ion
channels can change the resting potential.channels can change the resting potential.
► If changes cause the resting potential to beIf changes cause the resting potential to be
reduced, this is calledreduced, this is called depolarization.depolarization.
► If the change causes an increase in the restingIf the change causes an increase in the resting
potential, this is causedpotential, this is caused hyperpolarizationhyperpolarization ..
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8. Action potentialAction potential
► Voltage gated ion channels open and let Na+ into the cell.Voltage gated ion channels open and let Na+ into the cell.
They are driven into the cell because of diffusion gradientThey are driven into the cell because of diffusion gradient
and electrostatic charge.and electrostatic charge.
► This causes the resting potential to reverse, i.e., the insideThis causes the resting potential to reverse, i.e., the inside
the cell becomes positive.the cell becomes positive.
► Now the Na+ ion channels close and the K+ channels openNow the Na+ ion channels close and the K+ channels open
and the K+ ions are driven out of the cell because of theirand the K+ ions are driven out of the cell because of their
concentration gradient and electrostatic charge.concentration gradient and electrostatic charge.
► Finally the K+ channels close and the ion pumps kick inFinally the K+ channels close and the ion pumps kick in
and the resting potential returns to normal.and the resting potential returns to normal.
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10. All or None LawAll or None Law
►Action potentials when they occur areAction potentials when they occur are
always the same.always the same.
►Once the process is initiated, it must run itsOnce the process is initiated, it must run its
course and nothing can stop it or change itcourse and nothing can stop it or change it
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11. Transmission of action potentialsTransmission of action potentials
along a membranealong a membrane
►When an action potential occurs at oneWhen an action potential occurs at one
place on the membrane of an axon, theplace on the membrane of an axon, the
surrounding membrane is depolarized pastsurrounding membrane is depolarized past
threshold causing an action potential. Thisthreshold causing an action potential. This
depolarizes the neighboring membrane, etc.depolarizes the neighboring membrane, etc.
►Action potentials sweep across a membraneAction potentials sweep across a membrane
as fast as 100m/secas fast as 100m/sec
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12. 2 ) How does Botox work?
A) Inactivates AchE
B) Binds directly to the Ach receptor on the post-synaptic membrane
C) Generates antibodies directed against Ca++ channels located in presynaptic terminalsntibodies directed against Ca++ channels located in presynaptic terminals
D) Prevents the synaptic vesicle from exocytosis by degrading SNARE docking protein
1) Which of the following will produce an EPSP?
A) opening a sodium channel
B) closing a sodium channel
C) opening a potassium channel
D) closing a calcium channel
Questions
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13. A junction that mediates information transferA junction that mediates information transfer
from one cell to another, usually from onefrom one cell to another, usually from one
neuron:neuron:
To another neuronTo another neuron
To an effector cell (i.e. sweat gland, muscle cell)To an effector cell (i.e. sweat gland, muscle cell)
SynapsesSynapses
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15. Electrical SynapsesElectrical Synapses
Gap junctionsGap junctions made up ofmade up of
protein channels in the cellprotein channels in the cell
membrane calledmembrane called
ConnexonsConnexons allowallow Bi-Bi-
directionaldirectional flow of currentflow of current
between adjacent cells.between adjacent cells.
Found in cardiac and smoothFound in cardiac and smooth
muscle. Action potential ofmuscle. Action potential of
one cell causes actionone cell causes action
potential in next cell.potential in next cell.
Important in synchronizedImportant in synchronized
contractile activity.contractile activity.
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16. Chemical SynapsesChemical Synapses
presynaptic membrane
postsynaptic membrane
synaptic cleft
UsesUses
NeurotransmittersNeurotransmitters
released by actionreleased by action
potentials topotentials to
transmit signalstransmit signals
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17. Structure of a synapseStructure of a synapse
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18. From electrical to chemicalFrom electrical to chemical
1. Precursor transport1. Precursor transport
2. NT synthesis2. NT synthesis
3. Storage3. Storage
4. Release4. Release
5. Activation5. Activation
6. Termination6. Termination
Synaptic Transmission ModelSynaptic Transmission Model
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29. NeurotransmitterNeurotransmitter bindingbinding changes the receptor’s shape to open an ionchanges the receptor’s shape to open an ion
channel directlychannel directly
Fast acting and short lasting
Ionotropic receptors (ligand-gated)Ionotropic receptors (ligand-gated)
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30. Metabotropic receptors (G-protein)Metabotropic receptors (G-protein)
• indirect method
• located nearby G-proteins
• G-proteins in turn activate an
ion channel
• slower to begin and longer
lasting
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31. Metabotropic receptorsMetabotropic receptors
Second Messenger Cascade:
G-proteins can activate second
messengers – enzymes that in
turn activate an ion channel
Second messenger moleculesSecond messenger molecules
can activate acan activate a kinasekinase whichwhich
lasts for minutes and hours.lasts for minutes and hours.
Kinases can activateKinases can activate
transcription factorstranscription factors
(CREB and c-fos) which alter(CREB and c-fos) which alter
the expression of genes.the expression of genes.
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32. Post synaptic potentialPost synaptic potential
►Is the change in the resting potentialIs the change in the resting potential
((depolarization or hyperpolarization) caused bycaused by
the activation of a receptorthe activation of a receptor
Inhibitory post synaptic potential (IPSP) –Inhibitory post synaptic potential (IPSP) –
hyperpolarizes the cell making harder to firehyperpolarizes the cell making harder to fire
►K+K+ outout of cellof cell
►Or Cl-Or Cl- intointo cellcell
Excitatory post synaptic potential (EPSP) –Excitatory post synaptic potential (EPSP) –
depolarizing the cell making it more excitabledepolarizing the cell making it more excitable
►Na+Na+ intointo cellcell
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34. SummationSummation
Excitatory and inhibitoryExcitatory and inhibitory
potentials canpotentials can summatesummate
both in time (both in time (temporaltemporal
summationsummation) and across) and across
the membrane (the membrane (spatialspatial
summationsummation))
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35. Axoaxonic SynapsesAxoaxonic Synapses
► Modulate NT releaseModulate NT release
viavia ↓↓ oror ↑↑ CaCa2+2+
influxinflux
► Via modulation of EVia modulation of Emm
CaCa2+2+
, K, K++
, and Cl, and Cl--
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37. NEUROTRANSMITTERSNEUROTRANSMITTERS
Chemical transducersChemical transducers
released by electricalreleased by electrical
impulses into the synapticimpulses into the synaptic
cleft leading to alteration incleft leading to alteration in
electrical signalselectrical signals
50 different neurotransmitters50 different neurotransmitters
have been identifiedhave been identified
Loewi, 1921Loewi, 1921
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39. ► First neurotransmitter identifiedFirst neurotransmitter identified
► Synthesized and enclosed in synaptic vesiclesSynthesized and enclosed in synaptic vesicles
► DegradationDegradation
AcetylcholineAcetylcholine
Acetylcholine Choline + Acetate
Acetylcholine Esterase (AchE)
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40. Two types:
- Muscarinc
- Nicotinic
Binding of two Ach
molecules will rotate the
subunits causing the
influx of Na+ into the cell
and efflux of K+ resulting
in a depolarization of the
postsynaptic neuron and
the initiation of new action
potential.
Ach ReceptorAch Receptor
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41. Where it is FoundWhere it is Found
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42. NicotinicNicotinic MuscarinicMuscarinic
11 Found at:Found at:
i.i. Neuromuscular junction ofNeuromuscular junction of
skeletalskeletal musclemuscle
ii.ii. ALLALL preganglionicpreganglionic
neurons of the ANSneurons of the ANS
iii.iii. Ventral tegmental area.Ventral tegmental area.
i.i. Neuromuscular junctions ofNeuromuscular junctions of
cardiaccardiac andand smoothsmooth muscle.muscle.
ii.ii. Some postganglionicSome postganglionic
neurons of sympatheticneurons of sympathetic
nervous system (sweatnervous system (sweat
glands)glands)
22 AgonistAgonist NicotineNicotine Muscarine ( a toxin produced byMuscarine ( a toxin produced by
certain mushroom)certain mushroom)
33 AntagonistAntagonist Curare ( paralyses skeletalCurare ( paralyses skeletal
muscle)muscle)
AtropineAtropine
Acetylcholine ReceptorsAcetylcholine Receptors
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44. RECEPTORS DYSFUNCTIONRECEPTORS DYSFUNCTION
Presynaptic levelPresynaptic level
• Botulinum toxin: an exotoxin that binds to theBotulinum toxin: an exotoxin that binds to the
presynaptic membrane and prevents the release of Achpresynaptic membrane and prevents the release of Ach
resulting in weakness and reduction of toneresulting in weakness and reduction of tone
• Black widow spider venom:Black widow spider venom: stimulates release of Ach
• Lambert – Eaton syndrome: Antibodies directed againstLambert – Eaton syndrome: Antibodies directed against
CaCa++++
channels located in presynaptic terminals andchannels located in presynaptic terminals and
interfere with transmitter release causing weaknessinterfere with transmitter release causing weakness
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45. Postsynaptic levelPostsynaptic level
1.1. Curare binds to the acetylcholine nicotinic receptorsCurare binds to the acetylcholine nicotinic receptors
inducing paralysis.inducing paralysis.
2.2. Myasthenia gravis: antibody against Ach receptorsMyasthenia gravis: antibody against Ach receptors
and Ach receptors are reduced hence the Achand Ach receptors are reduced hence the Ach
released has few Ach receptor available to work andreleased has few Ach receptor available to work and
patients complain of weakness that increases withpatients complain of weakness that increases with
exerciseexercise
3.3. Insecticides/Organophosphates/Sarin: inhibit AchEInsecticides/Organophosphates/Sarin: inhibit AchE
(Pralidoxime and atropine used as antidote)(Pralidoxime and atropine used as antidote)
RECEPTORS DYSFUNCTION cont.RECEPTORS DYSFUNCTION cont.
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47. BIOGENIC AMINESBIOGENIC AMINES
► NorepinephrineNorepinephrine
Main NT of the sympathetic branch of autonomic nervous systemMain NT of the sympathetic branch of autonomic nervous system
Binds toBinds to adrenergic receptors (adrenergic receptors (αα oror ββ --many subtypes,many subtypes, αα11,, αα22, etc), etc)
Excitatory or inhibitoryExcitatory or inhibitory depending on receptor type bounddepending on receptor type bound
Release enhanced by amphetaminesRelease enhanced by amphetamines
Removal from synapse blocked by cocaineRemoval from synapse blocked by cocaine
► DopamineDopamine
Binds toBinds to dopaminergicdopaminergic receptors of substantia nigra of midbrainreceptors of substantia nigra of midbrain
and hypothalamusand hypothalamus
Release enhanced by amphetaminesRelease enhanced by amphetamines
Reuptake block by cocaineReuptake block by cocaine
Deficient in Parkinson’s diseaseDeficient in Parkinson’s disease
May be involved in pathogenesis of schizophreniaMay be involved in pathogenesis of schizophrenia
Azam BasheerAzam Basheer
50. Serotonin (5-HT)Serotonin (5-HT)
► Synthesized from a.a.Synthesized from a.a. tryptophantryptophan
► May play a role in sleep, appetite, and regulation ofMay play a role in sleep, appetite, and regulation of
moodsmoods
► Drugs that block its uptake relieve anxiety and depressionDrugs that block its uptake relieve anxiety and depression
SSRI’s = selective serotonin reuptake inhibitorsSSRI’s = selective serotonin reuptake inhibitors
Include drugs such as Prozac, Celexa, Lexapro, ZoloftInclude drugs such as Prozac, Celexa, Lexapro, Zoloft
Azam BasheerAzam Basheer
52. Gamma Aminobutyric acidGamma Aminobutyric acid
(GABA)(GABA)
► Universally inhibitory transmitterUniversally inhibitory transmitter
► Increases influx of Cl- in postsynaptic neuron,
hyperpolarising it and thus inhibiting it
► Drugs like benzodiazepines enhance the ability ofDrugs like benzodiazepines enhance the ability of
GABA to open the ion channel.GABA to open the ion channel.
► There are three types of GABA receptors e.g.There are three types of GABA receptors e.g.
GABAGABAA B & C.A B & C.
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54. ► Include:Include:
Substance P – mediator of pain signalsSubstance P – mediator of pain signals
Beta endorphin, dynorphin, and enkephalinsBeta endorphin, dynorphin, and enkephalins
► Act as natural opiates, reducing our perceptionAct as natural opiates, reducing our perception
of painof pain
Found in higher concentrations in marathoners andFound in higher concentrations in marathoners and
women who have just deliveredwomen who have just delivered
► Bind to the same receptors as opiates andBind to the same receptors as opiates and
morphinemorphine
Neurotransmitters: PeptidesNeurotransmitters: Peptides
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55. Glutamic acidGlutamic acid
►The most commonly foundThe most commonly found
neurotransmitter in the brain.neurotransmitter in the brain.
► It is always excitatory.It is always excitatory.
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56. When glutamate binds to NMDA (N methyl-D-aspartate)
receptors, ion channels open allowing Na influx and thus
depolarizaing the cell Azam Basheer
58. NeurotransmitterNeurotransmitter
PostsynapticPostsynaptic
effecteffect
Derived fromDerived from
Site ofSite of
synthesissynthesis
PostsynapticPostsynaptic
receptorreceptor
FateFate FunctionsFunctions
1.Acetyl choline1.Acetyl choline
(Ach)(Ach)
ExcitatoryExcitatory Acetyl co-A +Acetyl co-A +
CholineCholine
CholinergicCholinergic
nerve endingsnerve endings
CholinergicCholinergic
pathways ofpathways of
brainstembrainstem
1.1.NicotinicNicotinic
2.2.MuscarinicMuscarinic
Broken by acetylBroken by acetyl
cholinesterasecholinesterase
Cognitive functionsCognitive functions
e.g. memorye.g. memory
Peripheral action e.g.Peripheral action e.g.
cardiovascularcardiovascular
systemsystem
2. Catecholamines2. Catecholamines
i. Epinephrinei. Epinephrine
(adrenaline)(adrenaline)
Excitatory inExcitatory in
some butsome but
inhibitory ininhibitory in
otherother
TyrosineTyrosine
produced in liverproduced in liver
fromfrom
phenylalaninephenylalanine
AdrenalAdrenal
medulla andmedulla and
some CNSsome CNS
cellscells
Excites bothExcites both
alpha α &alpha α &
beta βbeta β
receptorsreceptors
1.1.Catabolized toCatabolized to
inactive productinactive product
through COMT &through COMT &
MAO in liverMAO in liver
2.2.Reuptake intoReuptake into
adrenergic nerveadrenergic nerve
endingsendings
3.3.Diffusion awayDiffusion away
from nerve endingsfrom nerve endings
to body fluidto body fluid
For details referFor details refer
ANS. e.g. fight orANS. e.g. fight or
flight, on heart,flight, on heart,
BP, gastrointestinalBP, gastrointestinal
activity etc.activity etc.
NorepinehrineNorepinehrine
controls attention &controls attention &
arousal.arousal.
ii.Norepinephrineii.Norepinephrine ExcitatoryExcitatory Tyrosine, foundTyrosine, found
in pons.in pons.
ReticularReticular
formation, locusformation, locus
coerules,coerules,
thalamus, mid-thalamus, mid-
brainbrain
Begins insideBegins inside
axoplasm ofaxoplasm of
adrenergicadrenergic
nerve ending isnerve ending is
completedcompleted
inside theinside the
secretarysecretary
vesiclesvesicles
αα11 αα22
ββ11 ββ22
iii. Dopamineiii. Dopamine ExcitatoryExcitatory TyrosineTyrosine CNS,CNS,
concentrated inconcentrated in
basal gangliabasal ganglia
and dopamineand dopamine
pathways e.g.pathways e.g.
nigrostriatal,nigrostriatal,
mesocorticolimmesocorticolim
bic and tubero-bic and tubero-
hypophysealhypophyseal
pathwaypathway
DD11 to Dto D55
receptorreceptor
Same as aboveSame as above Decreased dopamineDecreased dopamine
in parkinson’sin parkinson’s
disease.disease.
Increased dopamineIncreased dopamine
concentration causesconcentration causes
schizophreniaschizophrenia
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59. NeurotransmitterNeurotransmitter
PostsynapticPostsynaptic
effecteffect Derived fromDerived from
Site ofSite of
synthesissynthesis
PostsynapticPostsynaptic
receptorreceptor
FateFate FunctionsFunctions
3. serotonin3. serotonin
(5HT)(5HT)
ExcitatoryExcitatory TryptophanTryptophan CNS, GutCNS, Gut
(chromaffin(chromaffin
cells) Plateletscells) Platelets
& retina& retina
5-HT5-HT11 to 5-HTto 5-HT
77
5-HT5-HT 22 AA
receptor mediatereceptor mediate
plateletplatelet
aggregation &aggregation &
smooth musclesmooth muscle
contractioncontraction
Inactivated by MAOInactivated by MAO
to form 5-to form 5-
hydroxyindoleacetichydroxyindoleacetic
acid(5-HIAA) inacid(5-HIAA) in
pineal body it ispineal body it is
converted toconverted to
melatoninmelatonin
Mood control, sleep,Mood control, sleep,
pain feeling,pain feeling,
temperature, BP, &temperature, BP, &
hormonal activityhormonal activity
4. Histamine4. Histamine ExcitatoryExcitatory HistidineHistidine HypothalamusHypothalamus Three types HThree types H1,1,
HH2 ,2 ,HH33 receptorsreceptors
found infound in
peripheral tissuesperipheral tissues
& the brain& the brain
Enzyme diamineEnzyme diamine
oxidaseoxidase
(histaminase) cause(histaminase) cause
breakdownbreakdown
Arousal, painArousal, pain
threshold, bloodthreshold, blood
pressure, blood flowpressure, blood flow
control, gutcontrol, gut
secretion, allergicsecretion, allergic
reaction (involved inreaction (involved in
sensation of itch)sensation of itch)
5. Glutamate5. Glutamate ExcitatoryExcitatory
75% of75% of
excitatoryexcitatory
transmissiontransmission
in the brainin the brain
By reductiveBy reductive
amination ofamination of
Kreb’s cycleKreb’s cycle
intermediateintermediate
α –ketoglutarate.α –ketoglutarate.
Brain & spinalBrain & spinal
cord e.g.cord e.g.
hippocampushippocampus
Ionotropic andIonotropic and
metabotropicmetabotropic
receptors.receptors.
Three types ofThree types of
ionotropicionotropic
receptors e.g.receptors e.g.
NMDA, AMPANMDA, AMPA
and kainateand kainate
receptors.receptors.
It is cleared from theIt is cleared from the
brain ECF by Nabrain ECF by Na ++
dependent uptakedependent uptake
system in neuronssystem in neurons
and neuroglia.and neuroglia.
Long termLong term
potentiation involvedpotentiation involved
in memory andin memory and
learning by causinglearning by causing
CaCa++++
influx.influx.
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60. NeurotransmitterNeurotransmitter
PostsynapticPostsynaptic
effecteffect Derived fromDerived from
Site ofSite of
synthesissynthesis
PostsynapticPostsynaptic
receptorreceptor
FateFate FunctionsFunctions
6. Aspartate6. Aspartate ExcitatoryExcitatory Acidic aminesAcidic amines Spinal cordSpinal cord Spinal cordSpinal cord
Aspartate & Glycine form an excitatory /Aspartate & Glycine form an excitatory /
inhibitory pair in the ventral spinal cordinhibitory pair in the ventral spinal cord
7. Gama amino7. Gama amino
butyricbutyric
acid(GABA)acid(GABA)
MajorMajor
inhibitoryinhibitory
mediatormediator
DecarboxylationDecarboxylation
of glutamate byof glutamate by
glutamateglutamate
decarboxylasedecarboxylase
(GAD) by(GAD) by
GABAergicGABAergic
neuron.neuron.
CNSCNS
GABA – AGABA – A
increases the Clincreases the Cl --
conductance,conductance,
GABA – B isGABA – B is
metabotropicmetabotropic
works with G –works with G –
protein GABAprotein GABA
transaminasetransaminase
catalyzes.catalyzes.
GABA – CGABA – C
foundfound
exclusively inexclusively in
the retina.the retina.
Metabolized byMetabolized by
transamination totransamination to
succinate in the citricsuccinate in the citric
acid cycle.acid cycle.
GABA – A causesGABA – A causes
hyperpolarizationhyperpolarization
(inhibition)(inhibition)
Anxiolytic drugs likeAnxiolytic drugs like
benzodiazepine causebenzodiazepine cause
increase in Clincrease in Cl--
entryentry
into the cell & causeinto the cell & cause
soothing effects.soothing effects.
GABA – B causeGABA – B cause
increase conductanceincrease conductance
of Kof K++
into the cell.into the cell.
8. Glycine8. Glycine InhibitoryInhibitory
Is simple aminoIs simple amino
acid havingacid having
amino group andamino group and
a carboxyl groupa carboxyl group
attached to aattached to a
carbon atomcarbon atom
Spinal cordSpinal cord
Glycine receptorGlycine receptor
makesmakes
postsynapticpostsynaptic
membrane moremembrane more
permeable to Clpermeable to Cl--
ion.ion.
Deactivated in theDeactivated in the
synapse by simplesynapse by simple
process ofprocess of
reabsorbtion by activereabsorbtion by active
transport back intotransport back into
the presynapticthe presynaptic
membranemembrane
Glycine is inhibitoryGlycine is inhibitory
transmitted found intransmitted found in
the ventral spinalthe ventral spinal
cord. It is inhibitorycord. It is inhibitory
transmitter totransmitter to
Renshaw cells.Renshaw cells.
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