NewHumanPhysiology

| P a u l e v Z u b i e t a 2 n d E d i t i o n

C h a p t e r 1 : C e l l s a n d A c t i o n P o t e n t i a l s
HO ME

P RE FA CE

TA B L E O F CO NTE NTS

S Y MB O L S

S E CTI O N I NFO

CO NTRI B UTO RS

L I NK S

CO NTA CT US

Hi ghl i ghts

Chapter
1

S tudy_Obj ecti ves

P ri nci pl es
Defi ni ti ons
E ssenti al s

P athophysi ol ogy
E quati ons
S el fAssessm ent
Answers

Further Readi ng

StudyObjectives
T odefineac tiv ity ,ac tiv ity c oeffic ient,c onc entr ation,diffus ion,flux ,molality ,molar ity ,
nor mality ,os molality ,os mos is ,pr es s ur eandr adioac tiv ity .
T odes c r ibethediffus ionpotential,theequilibr iumpotential,fac ilitateddiffus ion,theD onnan

effec t,ther es tingmembr anepotential,theac tionpotential,andmembr anetr ans por tinc luding
thatofgluc os e.
T oc alc ulatetheequilibr iumpotential,os motic pr es s ur eandother v ar iables fr omr elev ant
v ar iables giv en.

T odr aw theac tionpotentialc ur v e.

T oex plainthec olloidos motic pr es s ur eofplas ma,hy ponatr aemia,ov er br eathing,r adioac tiv e
dec ay andtheeliminationr atec ons tant,thener v ec onduc tion,s ignaltr ans duc tion,thefunc tion
oftheac tionpotential,theN a + K + pumpandthetr ans por tpr oteins .
T ous etheidealgas law andtheabov ec onc epts inpr oblems olv ingandc as ehis tor ies .

Principles
T heidealgas law r elates thepr es s ur eP,thev olumeV,andthenumber ofmolofthegas n,to
theKelv intemper atur eT : PV=n*R*T.
Ats tandar dtemper atur e,pr es s ur e,dr y ( ST PD ) thev olumeoc c upiedby 1molofany idealgas
is 22.4litr e( l) . By analogy inanideals olution,onemolofs olutew illex er tanos motic
pr es s ur eofoneatmos pher e,ifitis dis s olv edin22.4lofw ater .Van tH off s law for ideal
s olutions is anequiv alenttotheidealgas law .

Definitions
A b so lu t eT em p erat u re( T ) is meas ur edinKelv inor Kfr omtheabs olutez er opoint( 273 o C ) .
Ac tiv ity is ac or r ec tedc onc entr ationmeas ur eofany s pec ies ( ie,thefr eec onc entr ationmultipliedby
theac tiv ity c oeffic ient) .T heac tiv ity is oftenmeas ur edw ithions elec tiv eelec tr odes . Indiluted
s olutions below 10 3 molar ther eis noc or r ec tionfor unc har gedmolec ules .
A ct ivit yco ef f icien t is thefr ac tionofthefr eeions ,w hic his c hemic ally ac tiv e. F or s odiumthe
ac tiv ity c oeffic ientis 0.75inmany biologic als olutions .
A ct io n Po t en t ial( AP) is anall or noneelec tr ic als ignal,w hic happear s as apos itiv ew av ew hen
r ec or dinginter nally .T heAPis c onduc tedw iththes ames hapeands iz ealongthew holelengthofa
mus c lec ellor aner v efibr e.
A m p h ip at h icm o lecu lesc ontainbothapolar andanon polar r egion.
T hem em b ran ep o t en t iald if f eren ceis definedas thepotentialins idethec ellminus thepotential
outs idethec ellthediffer enc eis tr ans iently r ev er s eddur inganAP.
B ecq u erel( 1Bq) is thepr efer r edunitfor dis integr ationr ateofr adioac tiv edec ay ,namely one

r adioac tiv edis integr ationper s .D is integr ationr ates w er epr ev ious ly ex pr es s edinC ur ies ( C i) ,in
honour ofMar ieC ur ie,w hodis c ov er edr adium.
C o n cen t rat io n ( C or br ac k ets ar oundas ubs tanc e[N a + ]) is themas s or moles ( mol) per unitoffluid
v olume.
D if f u sio n is anettr ans por tofatoms or molec ules c aus edby their r andomther malmotioninan
attempttoequalis ec onc entr ationdiffer enc es ( C ) .
T heD o n n an ef f ect is theex tr aos motic pr es s ur eofpr oteins olutions c aus edby imper meablepr otein
molec ules r es ultinginunev endis tr ibutionofs mall,per meantc ations andanions ( inbloodplas ma) .
T h eelim in at io n rat eco n st an t ( k ) is thefr ac tionofthetotalamountofagiv ens ubs tanc einthe
dis tr ibutionv olumeofthebody eliminatedper timeunit.Eliminationw ithac ons tantr ateis
ex ponential.T hehalf lifefor as ubs tanc eeliminatedex ponentially is equalto0.693k 1 .T his is jus ta
s implemathematic aldeduc tion.
F lu x( J ) is theamountofas ubs tanc etr ans por tedalongapr es s ur egr adientthr oughanar eaunit( A
is meas ur edinm 2 ) ofamembr aneinmoles per s ec ond( s ) .C onv ec tiv eflux is thenetamountof
molec ules tr ans por tedthr oughAper timeunit( mols 1 m 2 ) ,c aus edby apr es s ur egr adientandfluid
( liquidor air ) v olumetr ans por t.
Anid ealsem ip erm eab lem em b ran eis per meabletow ater only ,butimper meabletoalls olutes .Mos t
r eals emiper meablemembr anes ar eper meabletow ater andtolow molec ular s ubs tanc es
( c r y s talloids ) ,butnottomac r omolec ular s ubs tanc es ( c olloids s uc has pr oteins ) .
Mo larco n cen t rat io n ( molar ity ) is thenumber ofmoles ofas ubs tanc etotally dis s olv edper litr e( l) of
s olution oftengiv eninmmolper lor mM.O nemolofas ubs tanc eis theamountofthats ubs tanc e
c ontainingAv ogadr os number ,6.022*10 2 3 molec ules per mol.
Mo lalit yis thenumber ofmoltotally dis s olv eds ubs tanc eper k gofs olv ent,fr equently w ater .O ne
equiv alentis themolar mas s ofalltheions thatc ontain6.022*10 2 3 s inglec har ges or v alenc es w hen
fully dis s oc iated.
Mo t ilit yis ther ec ipr oc alr es is tanc eofamolec uletow ar ds mov ements .
N o rm alit yofas olutionis thenumber ofequiv alents per l( Eq l 1 ) .
O sm o lalit yis ameas ur eoftheos motic ac tiv epar tic les inonek gofw ater .Plas ma os molality is
giv eninO s molper k gofw ater .Water oc c upies 93% ofplas mainhealthy per s ons .
O sm o larit yis thenumber ofos motic ally ac tiv epar tic les dis s olv edinalitr eofs olution.
Ap erm eab lem em b ran eallow s thepas s ageofalldis s olv eds ubs tanc es andthes olv ent( mainly
w ater ) .
Aselect ivelyp erm eab lem em b ran eis per meabletoapar tic ular c ompound( s uc r os e,N a + ,C a 2 + ,
anions only or toc ations only ) .
Pressu re( P) is meas ur edas for c eper ar eaunit thatis inN ew tonper s quar emor Pas c al.
O sm o sisis tr ans por tofs olv entmolec ules ( mainly w ater ) thr oughas emiper meablemembr ane.
O sm o t icp ressu re( ) is thehy dr os tatic pr es s ur e,thatmus tbeappliedtothes ideofar igid
ideals emiper meablemembr anew ithhigher s olutec onc entr ationinor der tos topthew ater flux ,
s othatthenetw ater flux is z er o.
R ad io act ivit y.Somenuc leiar euns tableor r adioac tiv e,bec aus ethey r eleas ec er tainpar tic les
s uc has heliumnuc leior elec tr ons .O ther r adioac tiv es ubs tanc es emmanategamma r ay s w ith
anex tr emely s hor tw av elength.Allr adioac tiv edec ay pr oc es s es follow anex ponentialpatter n.
IfN o is theinitialnumber ofuns tablenuc lei,thenumber ofnuc leir emainingafter atimet( N ) is
giv enby N =N o *e k t ,w her ek is ac ons tantc har ac ter is tic ofeac hnuc lide,c alledthe
dis integr ationc ons tant.T his is thelaw ofr adioac tiv edec ay ( Eq .1 6) .
Vo lu m e( V) inlitr es ( l) .Standar dtemper atur e,pr es s ur e,dr y ( ST PD ) is anabbr ev iationfor a
v olumeats tandar dtemper atur eof273K,s tandar dpr es s ur eof101.3k Paor 760mmH g,and
dr y air .

Essentials

T hr eetopic s ar etr eatedher e:

1.T ran sp o rt t h ro u g h m em b ran es,2.R est in g m em b ran ep o t en t ials,and3.A ct io n p o t en t ials.

1.Transportthroughmembranes
Membr anetr ans por tr efer s tos oluteands olv enttr ans fer ac r os s bothc ellmembr anes ,epithelialand
c apillar y membr anes .
1a.Mem b ran es
Biologic almembr anes ar ec ompos edofphos pholipids s tabilis edby hy dr ophobic inter ac tions into
bilay er s ( F ig .1 1) .T hemembr anes c ontainappr ox imately 50% lipids and50% pr oteins .

c lic k ontheimagetos eealar ger v iew inanew w indow .

F ig .1 1: Mo d elo f acellm em b ran eb u ilt b yp h o sp h o lip id ssep arat in g recep t o rs,ch an n els,
p ro t ein s( Pr ) ,g lyco p ro t ein s( recep t o rs,an t ig en set c) an d g lyco lip id s.
Phos pholipids ar eamphipathic .O ner egionis polar c ons is tingofc har gedc holine,etanolamineand
phos phatehead gr oups ( bullets inF ig.1 1) .T heother r egionis non polar ,c ons is tingoftails offatty
ac y lc hains ( F ig.1 1) .T henon polar r egions tendtoav oidc ontac tw ithw ater by s elf as s oc iation.
Any other ar r angementw ithdis r uptionofhy dr ogenbonds ( betw eenO andH atoms ) ofw ater has a
highener gy c os t.Integr alpr oteins ar edeeply imbeddedinthemembr ane,andthemodels how s 3
pr oteinmolec ules s panningthemembr ane( ie,tr ans membr anepr oteins ) .Sur fac epr oteins ar enot
s how n.T hepr oteins c ar r y r ec eptor s tow hic htr ans mitter s ubs tanc ebind.C ar bohy dr atec hains ar e
s how nfor minggly c olipids w ithantigenic or r ec eptor func tion,or gly c opr oteins w ithother r ec eptor
func tions .
T hemolar c onc entr ation( molar ity ) is thenumber ofmoltotally dis s olv eds ubs tanc eper litr e( l) of
s olution oftengiv eninmmolper lor mM.Ions inplas maar ec onv entionally meas ur edinmMw ith
flame photometr y by theability toabs or bmonoc hr omatic light.N a + is mainly dis s olv edinthew ater
phas eofplas ma( 93% ) .T he[N a + ]inplas mais ther efor es maller thantheN a + ac tiv ity w hic his
r ec or dedinthew ater phas ealonew ithions elec tiv eelec tr odes .F or c onv entionalr eas ons ion
s elec tiv eelec tr odes ar ec alibr atedtomatc hthew ell k now nflamephotometr y v alues ,althoughthe
ac tiv ity is thebiologic alimpor tantv ar iable.Molality ,nor mality ,andflux ar edes c r ibedabov ein
D efinitions .
Mec hanic al,elec tr ic al,ther mal,or gr av itationalfor c es dr iv emigr ationofmolec ules .T hes efor c es
mov ethemolec ules pas s iv ely inadir ec tiondeter minedby thev ec tor ofthefor c e.
D iffus iv eflux ( J d i f ) is themov ementofmolec ules by diffus ionc aus edby ac onc entr ationgr adient
( dC /dx ) inthedir ec tionx .T hediffus ionc oeffic ient( D ) is apr opor tionality c ons tantthatr elates flux to
thec onc entr ationgr adient( dC /dx ) .Eins teindefinedD as ( k T B) ,w her eT is abs olutetemper atur e
andBis motility ofmolec ules .Motility is ther ec ipr oc alr es is tanc etow ar ds mov ements ( v eloc ity /N or
m*s 1 *N 1 ) .T hec onc ept( k *T ) is thether mal,molec ular ener gy .Amolec ulediffus es fr omhigher to
low er c onc entr ationthatis dow nits c onc entr ationgr adient.Ac c or dingly ,dC /dx has anegativ es lope,
w henmolec ules diffus einthedir ec tionx .T hen,itis eas y toc alc ulatethediffus iv eflux ( per m 2 )
ac c or dingtoEq .1 2.T his r elations hipw as fir s tr ec ogniz edas ear ly as in1855by theanatomis tand
phy s iologis tF ic k ,andithas s inc ebeennamedafter him:F ic k 's fir s tlaw ofdiffus ion.T heflux by
s implepas s iv ediffus ionis dir ec tly pr opor tionaltothec onc entr ationofdis s olv edmolec ules ( F ig .1
2) .

F ig .1 2: T w o t yp eso f p assivem o lecu lart ran sp o rt : Sim p led if f u sio n an d t h em u ch larg er

f acilit at ed d if f u sio n .C isco n cen t rat io n .
Eins tein's r elations tates thatfor av er agemolec ules inbiologic almedia,themeandis plac ement
s quar ed,( dx ) 2 ,is equalto2multipliedby D andby thetime( t) elaps ed,s inc ethemolec ules s tar ted
todiffus e( s eeEq .1 3) .F or molec ules w ithD =10 9 m 2 s 1 ,thetimer equir edtodiffus e1mis 0.5
milli s ec ond( ms ) .T odiffus e10and100m,thetimer equir edinc r eas es 100 foldeac htime:50ms
and5000ms .
F ac ilitateddiffus iontak es plac ethr oughtr ans por tpr oteins notlink eddir ec tly tometabolic ener gy
pr oc es s es ( F ig.1 2) .F ac ilitateddiffus ions how s s atur ationor Mic haelis Mentenk inetic s ,bec aus e
thenumber oftr ans por tpr oteins is limited.T hes atur ationk inetic s is differ entfr omtheener gy
limitationinpr imar y ac tiv etr ans por t.Aminoac ids ,gluc os e,galac tos eandother monos ac c har ides
c r os s many c ellmembr anes by fac ilitateddiffus ion.
Anideals emiper meablemembr aneis per meabletow ater only ,butimper meabletoalls olutes .Mos t
r eals emiper meablemembr anes ar eper meabletow ater andtolow molec ular s ubs tanc es
( c r y s talloids ) ,butnottomac r omolec ular s ubs tanc es ( c olloids s uc has pr oteins ) .
Anidealion s elec tiv emembr aneis per meabletoanions only or toc ations only ( N a + ,C a 2 + ,or toC l
andN O 3 ) .Ion s elec tiv emembr anes ar eus edinion s elec tiv eelec tr odes tomeas ur etheac tiv ity of
s elec tiv eions inplas maw ater ( T able1 1) .

Table11:Ionselectivemembranes
Select ivit y:

Eit h eran io n so rcat io n s

Sp ecif icit y:

C at io n m em b ran esd ist in g u ish b et w een N a + ,

C a 2 + ,an d K + .

A n io n m em b ran esd ist in g u ish b et w een C l

an d N O 3 .

T her elationbetw eenthepotentialdiffer enc emeas ur edw ithanion s elec tiv eelec tr odeandthe
ac tiv ity ( ionis edor fully dis s oc iatedfor m) for ac er tainion( eg,K + ) is giv enby theN er ns tequation
( Eq .1 5) .
1b .O sm o sisan d o sm o t icp ressu re
O s mos is is tr ans por tofs olv entmolec ules ( mainly w ater ) thr oughas emiper meablemembr ane.T he
w ater flow s fr omac ompar tmentofhighw ater c onc entr ation( or low s olutec onc entr ation) tooneof
low w ater c onc entr ation( or highs olutec onc entr ation) .T hegr eater differ enc ebetw eenthes olute
c onc entr ationofthetw oc ompar tments ,themor eis w ater unev enly dis tr ibutedbetw eenthetw o
c ompar tments .Water diffus es dow nits c hemic alpotentialgr adientintothec ompar tmentw ithhigher
s olutec onc entr ation,c aus ingthec hemic alpotentialgr adienttober educ eduntils oluteequilibr iumis
r eac hed.
O s motic pr es s ur eis thehy dr os tatic pr es s ur e,thatmus tbeappliedtothes ideofanideal
s emiper meablemembr anew ithhigher s olutec onc entr ationinor der tos topthew ater flux ,s othatthe
netw ater flux is z er o.
T hec olligativ epr oper ties ofw ater ar es tr ic tly r elatedtothes olv entor w ater c onc entr ationalone.
Water molec ules ar eboundtogether by hy dr ogenbonds inc lus ter s ofs ev er alhundr edmolec ules ,

for mingas tr uc tur elook ingalmos tlik ec r y s tals .Sites betw eenthec lus ter s ,w her ethedis tanc e
betw eenw ater molec ules ar elar ger thanels ew her ear ec alledbubblenuc leibec aus ethes es ites
s eemtoinitiatefor mationofgas bubbles indec ompr es s ions ic k nes s .T hes es ites ar eals olik ely
loc ations for s ubs tanc es dis s olv edinw ater .Withdec r eas ingw ater c onc entr ation,thew ater v apour
tens ion,andthefr eez ingpointis r educ ed,w her eas theboilingpoint,andtheos motic pr es s ur eofthe
s olutionis inc r eas edas c ompar edw ithpur ew ater .T hes iz eoftheos motic pr es s ur eofas olution
depends ofthenumber ofdis s olv edpar tic les per v olumeunit.
T heos motic pr es s ur e( ) depends ontheabs olutetemper atur e( T Kelv inor K) andonthenumber of
dis s olv edpar tic les per v olumeunit( N /Vequaltothemolar fr ac tion) .
T his r elations hipw as fir s tr ec ogniz edby v an'tH offandapplies toideals olutions only .R eal
phy s iologic als olutions ,s uc has thec y tos olic phas eandex tr ac ellular fluid,differ fr omtheideal
s olutions ,w hic har ev er y dilute.
Ac or r ec tionfac tor c alledtheos motic c oeffic ient( ) c or r ec ts for thes ediffer enc es inos molality .F or
phy s iologic elec tr oly tes itis 0.92 0.96,andfor c ar bohy dr ates itis 1.01.
As olutionhas theidealos molar ity one,w henitc ontains ( 6.022*10 2 3 ) os motic ally ac tiv epar tic les
per l.D iluteds olutions hav eanos molar c onc entr ationor os molar ity ( O s molper l) numer ic ally equal
tothes umtotalmolar ity ofalldis s olv edpar tic les ( molper l) .Inbiologic als olutions themolar ity is
differ entfr omos molar c onc entr ation.T henumber ofO s molper lis :( N /V) . T hec or r ec tedv an't
H offlaw is dev elopedinEq .1 4.
O s molality is s imply thenumber ofmolper k gofw ater inthefluidfr equently giv enas mO s molk g 1 .
F ully dis s oc iatedmolec ules hav etw ic etheos molality ofundis s oc iatedmolec ules .Plas ma os molality
c anbeappr ox imatedby thec alc ulationex pr es s edinEq .1 7.Plas ma os molality is meas ur edby
fr eez epointdepr es s ionor by boilingpointinc r eas e.T heos molality oftheIC Vis appr ox imately 290
mO s molk g 1 ,w hic his s implifiedto300mO s molk g 1 inF ig .1 4.T heos molality oftheex tr ac ellular
fluidmus tbethes ame,s inc ec ellmembr anes ar enotr igid,s othey c annotc ar r y any es s ential
pr es s ur egr adient.T hetotalnumber ofmO s molintheIC VandEC Vofas tandar dper s onis thus 8400
and4200,r es pec tiv ely ( F ig.1 4) .
T hec olloidos motic pr es s ur eis equalinmagnitudetothehy dr os tatic pr es s ur e,w hic hmus tbe
appliedattheluminals ideofthec apillar y bar r ier ,inor der tos topnettr ans por tofw ater c aus edby
unc har gedc olloids inthebloodplas ma.C olloids ar emainly plas mapr oteins .
T heos motic pr es s ur eis equalinmagnitudeofac er tainhy dr os tatic pr es s ur e.T his pr es s ur ec olumn
mus tbeappliedtothes olutiontor es tor ethefr eeener gy or c hemic alpotentialofits w ater tothatof
pur ew ater .T hetendenc y ofw ater topas s amembr anedepends onits c hemic alpotential( ie,v apour
pr es s ur e) .T hec hemic alpotentialofw ater dec r eas es w iths olutes pr es entandw ithdec r eas ing
temper atur e.
U nifor mly dis tr ibuteds ubs tanc es indiluteds olutions behav elik egas molec ules atatmos pher ic
pr es s ur e( atm) .T heos motic pr es s ur ec anbeex pr es s edas P o s m o t =C R T ,w hic his theequiv alent
oftheidealgas equation( PV=nR T ) .H er eC is thec onc entr ationofdis s olv eds olutes ,andthe
der iv ationofther elations hipis bas edonthec hemic alpotentialofw ater .R is thegas c ons tant( =
0.082latmO s mol 1 K 1 ) .Ats tandar dtemper atur e,pr es s ur e,dr y ( ST PD ) thev olumeoc c upiedby
1molofany idealgas is 22.4l.T hus ,ST PD is anabbr ev iationfor av olumeats tandar dtemper atur e
of273K,s tandar dpr es s ur eof101.3k Paor 760mmH g,anddr y air .Inanideals olution,onemolof
s olutew illby analogy bedis s olv edin22.4lofw ater ,andw illex er tanos motic pr es s ur eofone
atmos pher e.
Inbiologic als olutions at310K,s uc has anultr afiltr ateofplas ma( inter s titialfluid,ISF ) ,w ithan
os molality of0.300O s molper k gw ater ,theos motic pr es s ur emus tbe:
P o s m o t =0.3( O s molk g 1 ) 0.082( k gatmO s mol 1 K 1 ) 310( K) =7.63atm( =773k Pa) or
thepr es s ur eex er tedby ac olumnofw ater 76mhigh.
O nly netgr adients ac r os s endothelialandplas mamembr anes ar eimpor tant,andthey dependupon
pr oteinc onc entr ationgr adients .T his is bec aus ealltheelec tr oly tes ( c r y s talloids ) hav ediffus edto
equilibr iumac r os s thec apillar y endothelialmembr ane,w her eas pr oteins ( c olloids ) c annot.
T heav er agec olloidos motic pr es s ur e( c o l l ) ofplas mais appr ox imately 3.6k Pa( 27mmH g) .T he

dis s olv edpr oteins hav eamolality of1mmolper k gw ater ,andanetav er ageof17negativ ec har ges
per molec ule( ie,1mmolk g 1 or 17mEqk g 1 ) .Milli Equiv alents abbr ev iates mEq.T hepr oteins ar e
dir ec tly r es pons iblefor 2.4k Pa( 18mmH g) .T her emaining1.2k Pa( 9mmH g) ofthec olloidos motic
pr es s ur eis duetotheunequaldis tr ibutionofper meableions ,theG ibbs D onnanlaw or theD onnan
effec t( s eebelow ) .
1c.T h eD o n n an ef f ect acro sst h ecap illarym em b ran e
Letus c ons ider ac los eds y s temw ithtw oc ompar tments s epar atedby ar igidmembr anethatis
per meabletow ater andtos mallions .Inthepr es enc eofs olutions w ithdiffer entN aC lc onc entr ations ,
w ater andions per meater apidly inbothdir ec tions ac r os s themembr ane.Elec tr ic alneutr ality ineac h
ofthetw os olutions r equir es thatthes imultaneous mov ementofC l matc hany netmov ementofN a + ,
s otheequiv alents ofanions andc ations ar ethes ame.T henumber oftimes thetw oions c ollidew ith
ones ideofthemembr aneis pr opor tionaltothepr oduc toftheir c onc entr ations :[N a + ][C l ].At
equilibr iumtheflux es ofN aC lineac hdir ec tionar eidentic al,andultimately thec onc entr ations ar ethe
s ameallov er .
Letus now addpr oteintoonec ompar tment( c ompar tment p modellings tr eamingplas ma) ,w hic his
s epar atedby amembr ane( modellingthec apillar y endothelialmembr ane) fr omtheother c ompar tment
( c ompar tment I S F modellinginter s titialor tis s uefluid) .T hemodels tillc ontains only N a + andC l that
c anc r os s themembr ane.Atequilibr iumthepr oduc tofc onc entr ations ofthetw oions oneither s ide
ofthemembr anemus tbeequal,andthetr ans membr anepotentialc or r es ponds totheequilibr ium
potentialofthes mallper meantions ( theN er ns tequation,Eq 1 5) .T r ans for mingtheN er ns tequation
r ev eals thatthec onc entr ationpr oduc tofany pair ofdiffus ibleions is identic aloneither s ideofthe
membr aneatequilibr ium:
[N a + ] I S F [C l ] I S F =[N a + ] p [C l ] p .
O ntheplas mas ide,w hic hc ontains imper meantanions ( negativ epr oteinates ) ,thec onc entr ationof
per meantanion( C l is themodel) mus talw ay s beles s thanontheinter s titialfluids ide.T he
c onc entr ationofper meantc ation( N a + is themodel) mus talw ay s begr eater thanintheISF .
T hes umofper meantanionandc ationc onc entr ations inplas mais alw ay s gr eater thanthes umofthe
s ameanionandc ationc onc entr ations inISF :
[N a + ] I S F =[C l ] I S F [N a + ] p +[C l ] p >[N a + ] I S F +[C l ] I S F
T his is as implemathematic alar gument:T hes umofunequals ides ofar ec tangleis gr eater thanthe
s umofthes ides ofthes quar ew iththes amear ea.Itex plains w hy theos motic pr es s ur einplas ma
ex c eeds thatofthetis s uefluid.T his is notduetotheplas mapr oteins alone,butis als oduetothe
higher c onc entr ationofs mall,per meantions intheplas ma.
T heD onnaneffec tis theex tr aos motic pr es s ur eofpr oteins olutions c aus edby theunev en
dis tr ibutionofs mall,per meablec ations andanions .T heD onnaneffec tc aus es a5% and10%
c onc entr ationdiffer enc eac r os s thec apillar y bar r ier betw eentheplas maandultr afiltr ate
c onc entr ations ofmonov alentanddiv alentions ,r es pec tiv ely .
Intheabov eequations N a + andC l ar emodelions for allthec ations andanions .Inour body other
anions andc ations ar epr es ent,theN a + andC l c onc entr ations ar enotalik e,andthec apillar y
membr aneis far fr omr igid.N ev er theles s ,theD onnanequilibr iumimplies anac c umulationofc har ges
onthes idew iththenegativ ely c har gedpr oteins .T his potentialdiffer enc eac r os s thec apillar y
membr aneis ter medtheD onnanpotentialapotential,w hic his dev elopedac r os s c ellmembr anes
w ithoutas odium potas s iumpump.
T heD onnanfac tor atthec apillar y membr aneis 0.95,s oaplas ma N a + of150mmolmeas ur edin
eac hk gofplas ma w ater is inequilibr iumw ith142mMintheinter s titialfluidbetw eenthec ells .
Str ic tly s peak ing,ther eis nos uc hthingas ac ellw ithr igidc ellw alls intheanimalk ingdom,s othe
D onnaneffec tis theor etic ally unfoundedinanimalc ellmembr anes ex c eptatthec apillar y bar r ier .
1d .T h eN a + K + p u m p .
T heN a + K + pumpis atr ans membr anepr oteininthec ellmembr ane( F ig .1 3) .T hepumpc ontains a

c hannel,w hic hc ons is ts oftw odoubles ubunits :2 and2 s ubunits .T hec ataly tic s ubunit( ) is
anN a + K + ac tiv atedAT Pas eof112000D alton,andthe s ubunitis agly c opr oteinof35000D .

F ig .1 3: T h eN a + K + p u m p co n sist so f 2 an d 2 su b u n it s( Pi=Ph o sp h at e) .
T hepumpis apr imar y ac tiv etr ans por ter ,bec aus eitus es thec ellular ener gy oftheter minal
phos phatebondofAT P( F ig.1 3) .T heN a + K + pumptr ans por ts 3N a + outofthec elland2K + intothe
c ellfor eac hAT Phy dr oly s ed.T his is anetmov ementofpos itiv eions outofthec ell,andther efor e
c alledanelec tr ogenic tr ans por t.T hec ons tantinflux ofN a + is s how nas w ellas theleak ageofK +
andC l .Inas teady s tatethenettr ans por tofeac hionac r os s ther es tingmembr aneis z er o.
T heN a + K + pumpis loc atedinthebas olater alex it membr aneoftheepithelialc ell( F ig .1 3) .T he
pr imar y ac tiv eion tr ans por tpr ov ides metabolic ener gy for thes ec ondar y w ater abs or ptionthr ough
theluminalmembr ane.H er eby ,theac tiv epumpintheex it membr anedr iv es theluminaltr ans por t
ac r os s theentr y membr ane.T his tr ans por tofN aC landw ater is s ur pr is ingly near ly is otonic .T hebulk
flow c antak eplac eagains talar geos motic gr adient,andinc r eas es indiluteds olutions .T heentr y
membr aneis oftenhighly per meabletow ater .
T heN a + K + pumpbuilds upahighc ellular elec tr oc hemic algr adientfor K + andindir ec tly for C l ( F ig .
1 3) .T hew ater outflux is c oupledtotheoutw ar dtr ans por tofK + andC l .T heinter s titialfluidr ec eiv es
ions andgluc os e,c aus ingits os molar ity toinc r eas e.T heos motic for c ec aus es w ater toenter the
inter s titialfluidv iathec ellmembr anes andthegaps betw eenthec ells ( tightjunc tions ) .T his intur n
c aus es thehy dr os tatic pr es s ur eintheinter s titialfluidtor is e.T hehy dr os tatic for c etr ans fer s the
bulk ofw ater ,ions andmolec ules thr oughthethin w alled,tubular c apillar ies totheblood.When
ex c es s ofw ater ( s olv ent) pas s es thr oughtightjunc tions ,they los epar toftheir tightnes s andthe
s olv entw ater dr ags many N a + /C l ions out( s olv entdr ag) .
Inahealthy s tandar dper s onnutr ients andox y genar etr ans por tedintothec ellinter ior fr omthe
ex tr ac ellular fluidthr oughthec ellmembr ane( F ig .1 4) .T heintr ac ellular fluidv olume,IC V,is 26 28l.
T heex tr ac ellular fluidv olume( ie,EC Vof14l) c ons is ts ofthec ir c ulatingbloodplas ma( 3 3.5l) and
theinter s titialfluid( ISF ) w ithav olumeof10.5 11linthes pac es betw eenc ells .T otalbody w ater
( her e42l) ac c ounts for 60% ofbody w eight.T hebody is c lear edof24molofc ar bondiox ideby the
lungs in24hour s andofother s ubs tanc es by thek idney s ( F ig.1 4) .Ay ellow tubeonthediagr am
s y mbolis es thegas tr ointes tinalc hannel,w her enutr ientmolec ules ar eabs or bedandw as tepr oduc ts
ar eeliminatedthr oughtheliv er bile.

F ig .1 4: Salt an d w at er t ran sp o rt t h ro u g h acellm em b ran esep arat in g t h ein t racellu laran d

ext racellu larco m p art m en t .
T hediagr amals os how s theN a + K + pumptogether w ithleak ageofK + ,C l andw ater ( F ig.1 4) .T he

nettr ans por tofeac hs ubs tanc eis z er ointhes teady s tate.
T heN a + K + pumpis r es pons iblefor maintainingthehighintr ac ellular [K + ]andthelow intr ac ellular
[N a + ].T heener gy oftheter minalphos phatebondofAT Pis us edtoac tiv ely ex tr udeN a + andpumpK +
intothec ell.
J ens C hr is tianSk ouofD enmar k initiatedthes tudy oftheN a + K + pumpalr eady inthe1950ties and
r ec eiv edtheN obelPr iz efor his c ontr ibutiontobas ic c hemis tr y andphy s iology in1997.
T hemembr aneals oc ontains many K + andC l c hannels ,thr oughw hic hthetw oions leak thr oughthe
c ellmembr ane.
Intes tinalandk idney tubulec ells tr ans por ts ubs tr ates ,s uc has gluc os eandaminoac ids ,ina
s ubs tr ate N a + c otr ans por tintheluminalmembr ane,link edtotheN a + K + pumpofthebas olater al
membr ane.T his is c alledas ec ondar y ac tiv etr ans por tofs ubs tr ate.Suc hatr ans por tis pow er edby
anac tiv ely es tablis hedgr adient( ie,theN a + gr adient)
T hemany ion tr ans por tingAT Pas es for mc las s es or families s how ingaminoac ids equenc ehomology .
1e.G lu co set ran sp o rt p ro t ein s( G L U T s) an d in su lin recep t o rs
Afamily ofhomologous c ar r ier pr oteins thatar ec odedby dis tinc tgenes mediates gluc os e tr ans por t.
T hetr ans por tpr oteins ( G LU T s ) s how amar k edtis s ue s pec ific ity ,w hic hr eflec ts differ ingtr ans por t
needs ofv ar ious tis s ues .T his is fac ilitatedtr ans por t( F ig .1 2) .
F iv ehumangluc os e tr ans por ter s ar ec lonedandidentified( G LU T 1 5) .T heG LU T 1r es ides in
plac enta,br ain,per ineur als heaths ,r edc ells ,adipos eandmus c letis s ues .G LU T 2is foundinthe
liv er ,panc r eatic c ells ,pr ox imalr enaltubulec ells ,andthebas olater almembr anes ofs mall
intes tinalc ells .G LU T 3is ubiquitous ly dis tr ibuted,foundpr edominantly inthebr ainandinlow er
c onc entr ations infat,k idney ,liv er andmus c letis s ues .G LU T 4is c onfinedtotis s ues w ithins ulin
r es pons iv egluc os euptak e( mus c le,hear tandfats tor es ) .G LU T 5is foundintheluminalmembr ane
ofs mallintes tinalc ells ,andals oinbr ain,mus c leandadipos etis s ues .Someofthes etr ans por ter s
als oallow fr uc tos eandgalac tos etopas s .

F ig .1 5: In su lin ,in su lin recep t o rs,w it h D g lu co set ran sp o rt p ro t ein s( G L U T s) an d t h eir

t ran slo cat io n .
Inadipoc y tes andmus c lec ells ,gluc os etr ans por tis pr ofoundly influenc edby ins ulin( F ig.1 5) .
1.As ins ulinbinds toits lar geT s hapedins ulinr ec eptor ,many intr ac ellular v es ic les ar e
s timulated.
2.T hey c ontainahighnumber ofmembr anepenetr atingG LU T s ,w hic htr ans loc atefr omthe
intr ac ellular pooltow ar ds thec ellmembr ane.
3.Whenthes ev es ic les r ic hingluc os etr ans por ter s fus ew iththec ellmembr ane,thenumber
ofgluc os etr ans por ter s inc r eas es s ubs tantially ,ther eby inc r eas ingD gluc os euptak euptoten
times .
4.As theins ulin r ec eptor c omplex dis s oc iates ,theG LU T s tr ans loc ateagaintotheintr ac ellular
s tor es inthev es ic les ( F ig .1 5) .
5.T hegluc os etr ans por tc eas es .
T heins ulinr ec eptor is agly c opr oteinfoundinthec ellmembr anes .T heT s hapedr ec eptor pr otr uding
fr omthec ellmembr anec ontains 1370aminoac ids for mingtw o andtw o s ub units .T hetw o
s ubunits ar eentir ely ex tr ac ellular ,w her eas thetw o s ubunits s panthemembr ane.Ins ulinbindingon

 s ubunits s timulates apr oteink inas eontheintr ac ellular par tofther ec eptor tophos phor y late
ty r os iner es idues onthe s ubunitandonendogenous pr oteins .T heex ac tmolec ular mec hanis m
link ingther ec eptor k inas eac tiv ity toc hanges inc ellular enz y meac tiv ity andtr ans por tpr oc es s es
r emainunc er tainbutitis s how nthatthek inas eac tiv ity is es s entialfor s ignaltr ans duc tion.

2.Restingmembranepotentials
Amembr anepotentialdiffer enc eis c onv entionally definedas theintr ac ellular ( i ) minus the
ex tr ac ellular ( o ) elec tr ic alpotential.T heionc onc entr ations ( ac tiv ities ) ins idethec ellandouts ide
thec ellar ec alledC i andC o ,r es pec tiv ely .
Whenamic r oelec tr odepenetr ates amembr ane,itr ec or ds anegativ epotentialw ithr es pec ttoan
ex ter nalr efer enc eelec tr odec aus edby differ entper meability ofanions andc ations .T his is the
r es tingmembr anepotential( R MPv alues inT ab le1 2) .T her es tingmembr anepotentialis an
es s entialmec hanis mins tor ingandpr oc es s inginfor mationinneur ons andother c ells .
C onc entr ationgr adients ac r os s c ellmembr anes ar epr es entfor s ev er alions ,w her eby they diffus e
fr omoneloc ationtoanother .T heionw iththehighes tper meability andc onc entr ationgr adient,s uc h
as thepotas s iumion,es tablis hes amembr anepotential.T his potentialenhanc es or inhibits theflux of
other ions andtheultimates ituationis anelec tr oneutr alflux .
T hec hlor ideiondiffus es ex tr emely r apidly ,butother w is epos itiv eions ( c ations ) diffus emor er apidly
thannegativ eions ( anions ) thr oughamembr ane.H ow ev er ,as anex ampletheper meability for N a + is
low ( 0.2nm*s 1 ) c ompar edtothatofK + ( 5 40nm/s ) inneur ons .
T heequilibr iumpotentialfor ac er taindiffus ibleionac r os s amembr anethathas ac onc entr ation
gr adientov er themembr ane,is pr ec is ely thatmembr anepotentialdiffer enc e,w hic hoppos es theflux
duetothec onc entr ationgr adients othatthenettr ans por toftheionc onc er nedis z er o.T he
equilibr iumpotentialis s imply c alc ulatedby balanc ingthediffus ionpotentialoftheionw iththe
oppos ingelec tr ic alfor c e.T heelec tr ic alfor c ew or k ingontheionis pr opor tionaltotheelec tr omotiv e
for c eofthefield.As ac ons equenc e,thetotaldr iv ingfor c eontheionandits diffus ionflux is z er o.
N er ns tintr oduc edthis equilibr iumpotentials hor tly befor ey ear 1900.T heN er ns tequationfor the
equilibr iumpotentialofN a + ac r os s as elec tiv eper meablemembr aneat310Kis foundby ins er tionof
theionac tiv ities ( c onc entr ations ) ins ideandouts idethec ell( Eq .1 5) .
T ab le1 2: R est in g m em b ran ep o t en t ials( R MP) an d eq u ilib riu m p o t en t ials( V E q ) in d if f eren t
cells.

R MP( m V)

V E q ( m V)

R es tings k eletalmus c le

80

80for C l

andmy oc ar dialc ells

90

94for K +

+60for N a +

+130for C a 2 +

Smoothmus c lec ells

40to60( os c illations )

Var iable

N eur ons

70

As abov e

Ins k eletalmus c lec ells ther es tingmembr anepotentialis 80mV,andtheequilibr iumpotentialofN a +

is +60mV.H enc e,theelec tr ic aldr iv ingfor c eis :( 80 ( +60) ) = 140mVolts .Ac c or dingly ,ther eis a
netpas s iv einflux ofN a + intothes ec ells dow nanelec tr oc hemic algr adient( T able1 2) .T henetinflux
is s mallbec aus ether es tingN a + penetr ationis almos tex ac tly balanc edby ac tiv eex tr us ion.
T her es tingmembr anepotential( R MP) is c alc ulatedfr omtheMillmanequation( Eq .1 8) .T heR MPis
mainly adiffus ionpotential( s eeabov e) .
N eur ons ty pic ally hav efour s tr uc tur es :T hec ellbody ,dendr ites ,ax onandax onter minals ( F ig .1 6) .
D endr ites ar eelabor atebr anc hingpr oc es s es thatar is efr omthec ellbody ,andthey ar epathw ay s for
inc omings ignals fr omother neur ons tothec ellbody .Integr ationofinc omings ignals oc c ur s mainly in
theax onhilloc k .T his is thepar tofthec ellbody ,w hic hgiv es r is etoanelongatedtubec alledan
ax on,afibr ethatc anbeupto1.2mlong.

F ig .1 6: T h en eu ro n w it h cellb o d y,d en d rit es,axo n an d axo n t erm in als.

N ear its ter minationeac hax ondiv ides intofinebr anc hes ,eac hofw hic hends inanax onter minal( ie,
s y naptic buttonor Boltonter minal) .T heax onter minals c ontainmitoc hondr iaands y naptic v es ic les
filledw ithneur otr ans mitter .T hes epr es y naptic s tr uc tur es ar ethes ites w her eelec tr ic als ignals ar e
c onv er tedintoc hemic almes s ages for tr ans mis s iontonear by neur ons .U nipolar neur ons only hav ea
s inglemajor pr oc es s ex tendingfr omthec ellbody .Bipolar andmultipolar neur ons hav etw oor mor e
major pr oc es s es ar is ingfr omthec ellbody .Mos tneur ons hav eonly oneax on,afew mor ethanone
ands omeneur ons func tionw ithoutanax on.T heir loc ation,s tr uc tur eandfunc tionalpr oper ties ( T ab le
3 1) c las s ify neur ons .C ommunic ationfr omanax ontoadendr iteis c alledax odendr itic ,fr oma
dendr itetoanother is ter meddendr o dendr itic ,fr omadendr itetoanax onis c alleddendr o ax onal,
fr omadendr itetothes omais c alleddendr o s omatic ,andbetw eentw oax ons is r efer r edtoas ax o
ax onal.
N eur onalmembr anes ar ec ompos edoflipidbilay er s s tabilis edby hy dr ophobic inter ac tions ,andthus
func tionas bar r ier s tofr eediffus ionfor w ater s olublemolec ules .T heability oftheneur onal
membr anetoc ontr olthemov ementandc onc entr ationofc har gedpar tic les gener ates iongr adients
w ithac har gediffer enc eac r os s themembr ane.T hepotentialdiffer enc eac r os s ther es tingmembr ane
is c alledther es tingmembr anepotential( R MP) .
Ionc hannels andgates ar ec las s ifiedac c or dingtothegatings timulus tow hic hthey r es pond.
Voltage gatedionc hannels ar eloc atedalongtheax onofaneur onandr es pons iblefor theac tion
potential.T hes eionc hannels ar es ens itiv etoloc alanaes thetic s .Voltage gatedN a + K + andC a 2 +
c hannels c ontainmembr anes panninghelic es oftenw ithaminoac ids equenc ehomology .Ac tion
potentials inc ar diac mus c lec ells hav eaplateauphas e,w her eC a 2 + enter s thec y tos olv ias low
C a 2 + c hannels .T his C a 2 + entr y play s animpor tantr oleinex c itation c ontr ac tionc oupling.
Ligand gatedionc hannels ar er es pons iv etopar tic ular neur otr ans mitter s .Ligand gatedionc hannels
openinr es pons etos ubs tanc es s uc has ac ety lc holine.T hes ec hannels ar eper meabletos mall
c ations ( oftenuns elec tiv ely :N a + K + N H 4 + andC a 2 + ) .T hes ec hannels ar einv olv edingener ationof
thepos ts y naptic potentialandtheendplatepotential.
N aC lis foundinhighc onc entr ationouts idetheneur ons ,w her eas K + is highins idethec ell.T hes e
iongr adients maintainac ons tantleak ageofN aC lintothec ell,andaleak ageofK + out.T hegr adients
ar emaintainedby theN a + K + pump,w hic his thus c ontr ollingther es tingmembr anepotential.C l
ions dis tr ibutes pas s iv ely ac r os s mos tneur onalmembr anes andc ontr ibutes littletother es ting
membr anepotential,butthey ar eimpor tantfor themodulationofinc omings ignals .Atr es t,many K +
c hannels ar eopenandK + mov es dow nits c onc entr ationgr adientoutofthec ell,w her eby theins ide
bec omes negativ ely c har ged( untilitis diffic ultfor K + toleav ethec ell,andtheK + outflux s low s
dow n) .T heR MPappr oac hes theequilibr iumpotentialfor K + .

3.Theactionpotential
N eur ons c anc ar r y elec tr ic als ignals alongtheir w holelengthw ithoutany los s ofs ignals tr ength.T his
elec tr ic als ignalis anall or nonephenomenon,ter medtheac tionpotential.T heinc omings ignals to
dendr ites andc ellbodies c ons is tofs mall,gr adedc hanges ( ie,s malls y naptic potentials ) inthe
r es tingmembr anepotentialc aus edby theac tions ofneur otr ans mitter s andmodulator s .Sy naptic
potentials ar es patially andtempor ally s ummatedintheax onhilloc k ofthec ellbody .T hes y naptic
potentialis gr adedac c or dingtothes timulus ands how s dec r ementc onduc tioninthatits s iz e
dec r eas es w ithinc r eas ingdis tanc e( w av elengths ev er almm) .T heloc als y naptic potentialc annotin

its elfinitiateanac tionpotential.Whenthes tr engthofthes ummateds y naptic potentials is s uffic ient

tor educ ether es tingmembr anepotentialattheax onhilloc k below thethr es holditopens N a +
c hannels .T hes eN a + c hannels ar ev oltage gated,bec aus ethec hangeinv oltageopens or c los es a
gateov er eac hpor e.T heN a + c hannels is us ually c los edatc onditions w ithanor malr es ting
membr anepotential.WhentheN a + c hannels openandallow N a + toflow intothec elldow nits
c onc entr ationgr adient,theinflux its elfdepolar iz es theneur onfur ther ,w her eby mor ev oltage gated
N a + c hannels open.Apr opagatingac tionpotential( appr oac hes theequilibr iumpotentialfor N a + ) in
theax onis gener atedw ithapos itiv ev oltageov er s hoots imultaneous ly w iththepeak membr ane
c onduc tanc etoN a + ( g N a + inF ig .1 7) .T his is follow edby ther epolar is ationphas e( c onduc tanc efor
N a + goes dow nandupfor K + ) ,w henthepotentialr etur ns tow ar dther es tingmembr anepotential.T he
potentialmay ov er s hootther es tingv alue,c aus ingatr ans ienthy per polar iz ationk now nas the
hy per polar is ingafter potential( F ig .1 7) c los etotheequilibr iumpotentialfor K + .
Sus taineddepolar iz ationinac tiv ates thev oltage gatedN a + c hannels ,ands huts offtheN a + influx .
O peningofv oltage gatedK + c hannels allow s aninc r eas edoutflux ofK + toc ounter balanc etheinflux
ofN a + .T hemembr anec onduc tanc etoK + inc r eas es s low ly ,andr eac hes apeak inther epolar iz ation
phas e( g K + inF ig.1 7) .T his K + outflux c aus es theneur onalmembr anepotentialtor etur ntoits
nor malr es tingv alue,w hentheN a + c hannelis inac tiv ated.T hes ignalc onduc tionis unidir ec tional,
bec aus enew ly openedN a + c hannels bec omer efr ac tor y for atime,w henthey ar einac tiv ated.As
thes ear eas ar ebloc k edfor fur ther depolar iz ationfor atime,thedepolar iz ationc anpr oc eedonly in
thefor w ar ddir ec tiontow ar ds r es tingN a + c hannels .

F ig .1 7: T ran sm em b ran ep o t en t ialsan d N a + K + co n d u ct an ce( f lu x) in an eu ro n .

T heac tionpotentialis anall or noneelec tr ic als ignal,w hic happear s as apos itiv ew av ew hen
r ec or dinginter nally .T heac tionpotentialis c onduc tedw iththes ames hapeands iz ealongthew hole
lengthofamus c lec ellor aner v efibr e.
T h eref ract o ryp erio d s
D ur ingtheear ly par toftheac tionpotentialthec ellmembr aneis c ompletely r efr ac tor y .Anew
s timulus ,r egar dles s ofits s iz e,c annotev ok eanac tionpotential.Almos tallN a + c hannels ar e
inac tiv ated,andw illnotr eopenuntilthec ellmembr aneis r epolar iz ed.T his is theabs oluter efr ac tor y
per iodc ov er ingmos tofthepeak andlas tinguntilw ellintother epolar iz ingphas e( AR PinF ig.1 7) .
D ur ingthehy per polar iz ingafter potential,as upr athr es holds timulus is abletotr igger anew AP,albeit
ofs maller amplitudethanthefir s tac tionpotential.T his per iodis c alledther elativ er efr ac tor y per iod
( R R PinF ig .1 7) .T hec ellmembr aneis r elativ ely r efr ac tor y ,bec aus es omeN a + c hannels ar e
v oltage inac tiv atedandatthes ametimeK + c onduc tanc eis inc r eas ed.
N erveco n d u ct io n
T helipophilic c or eofthec ellmembr aneis anelec tr ic alins ulator ,butthes alts olutions ofthe
c y toplas mandtheex tr ac ellular fluidac tas c onduc tor s ofelec tr ic alc ur r ent.O peningofmany
v oltage gatedN a + c hannels ,w her eby theN a + c onduc tanc eis inc r eas edabout104 fold,s othe
membr aneis ins tantly depolar is ed,c aus es theac tionpotential.T heac tionpotentiales s entially
s pr eadby alter ations ofthev oltage gatedN a + c hannels .
D epolar iz ations pr eads alongthemembr aneofex c itablec ells by loc alc ur r ents flow ingtothe
adjac ents egments ofthemembr ane.T his is s how ninF ig .1 8A .T hephenomenonis c alledtheloc al

r es pons eor elec tr otonic c onduc tion.T hedepolar iz ationdec r eas es mono ex ponentially fr omthe
ex c itations ite.N a + c hannels w illber ec r uitedinallar eas ofthemembr ane,w her ethethr es hold
potentialis ex c eeded.T heN a + c hannels behindthepeak oftheac tionpotentialar er efr ac tor y .T his
ex plains w hy anac tionpotentialtr av els inbothdir ec tions ,w henitis ev ok edinthemiddleofaner v e.

F ig .1 8: Sp read o f t h eact io n p o t en t ialalo n g an u n m yelin at ed ( A ) an d am yelin at ed ( B ) axo n .

T h eref ract o rych an n elsp reven t t h eact io n p o t en t ialf ro m p ro ceed in g in m o ret h an o n e
d irect io n .T h eact io n p o t en t ial( w avelen g t h in cm ) essen t iallyju m p sf ro m n o d et o n o d eo r
o verseveraln o d esf acilit at in g h ig h sp eed co n d u ct io n .
T hemy elins heathc ons is ts of20 300lay er s ofins ulator s ubs tanc epr oduc edby Sc hw annc ells
w r appingr oundtheax on.T henodes ofR anv ier ar ethelater als pac es ( 1mw ide) betw eenadjac ent
Sc hw annc ells ,w hic hs tr etc h1 2mm.
T heeffec ts ofthis ar r angementar eas follow s :
Ver y littlec ur r entis los tthr oughtheelec tr ic alins ulationofthemy elins heath.T hus ,theelec tr otonic
c onduc tionis r apidw ithonly as malldec r ementinamplitude.T heelec tr otonic c onduc tionis v ir tually
ins tantaneous .Bec aus eoftheins ulationthedepolar iz ationc ans pr eadmuc hfas ter .
Saltator y or leapingc onduc tionoc c ur s ,bec aus etheac tionpotentialis gener atedonly atthenodes
( F ig .1 8) .T hec ellmembr anebelow themy elins heaths has har dly any N a + c hannels andis
ther efor einex c itable.Saltator y c onduc tionis upto50times fas ter thanthec onduc tionthr oughthe
fas tes tunmy elinatedax ons .T heac tionpotentialc anals ojumpov er anumber ofnodes tothat
far thes taw ay ,bec aus etheac tionpotentialw av elengthis s ev er alm.
T heN a + c hannels ther ear eac tiv atedby theelec tr otonic c onduc tion.
Sinc etheionic c ur r ents ar er es tr ic tedtothenodes ofR anv ier inthemy elinatedax ons ,this
minimis es dis tur banc es intheN a + andK + gr adients ,thatar er es tor edby anac tiv epr oc es s inw hic h
theN a + K + pump,dr iv enby AT P,pumps N a + outandK + intothec ell.T hemainener gy c os tis to
r es tor etheN a + K + balanc e.
My elinationofthener v efibr ethus r educ es ener gy c os tofmaintainingther es tingmembr anepotential
follow inganac tionpotential.
T y pic alv alues for nor malionc onc entr ations ( intr ac ellular ly andex tr ac ellular ly ) ar egiv eninT able1
3.
T ab le1 3: N o rm alio n co n cen t rat io n sin m u sclecellsan d in p lasm a.
In t racellu laro sm o lalit y
m m o l*( kg o f w at er) 1

Plasm aco n cen t rat io n ran g es

m m o l*( lo f p lasm a) 1

Na+

10

135 146

K+

155

3.5 5.0

Ca2+

0.0001

11.2

Mg 2 +

12

0.71.1

C l

95106

HCO 3

10

22 27

T hetotalc alc iumc onc entr ationinplas mais 2.22.7mM,butonly 45% is ioniz ed( C h ap t er30) .

Pathophysiology
T his par agr aphdeals w iths implec onditions ,w her ethes tudentneeds nopr ior k now ledge,s oonly
hy ponatr aemia,ps eudo hy ponatr aemiaandov er br eathingar edes c r ibed.
1.H y ponatr aemiais definedas aplas ma N a + below 135mM.T his is ac ommonc onditionc aus edby
ahighw ater intak e( w ater intox ic ation) ,r educ edw ater ex c r etionink idney dis eas e,s altlos s or other
c aus es des c r ibedinC h ap t er24.
H y ponatr aemiamus tbedis tinguis hedfr omther ar ec onditionps eudo hy ponatr aemia.Spur ious ly low
N a + ar emeas ur edinplas ma( N a + is pr edominantly c onfinedtothew ater phas e) ,s imply bec aus eits
c onc entr ationis ex pr es s edper lofplas ma.N or mally ,93% ofplas mais w ater ,andthenon w ater
fr ac tionis 7% ( mainly pr oteins ) .Inc as es w ithtoomuc hlipid,pr otein,gluc os e,ur ea,or alc oholinthe
bloodplas ma( ie,hy per lipidaemia,hy per pr oteinaemia,hy per gluc os aemia,ur aemia,alc oholaemiaetc ) ,
thenor malN a + is r educ edby dilutionw iththeinc r eas ednon w ater fr ac tion.T hus ,thec alc ulated
plas ma os molality ( Eq .1 7) is les s thanthefr eez e point meas ur edos molality .T his dis c r epanc y is
c alledtheos molality gap.
T her eis noneedfor tr eatmentw iths alt s olutions ins uc hs pur ious c onditions .Ps eudo hy ponatr aemia
als ooc c ur s ,w henabloods ampleis tak enfr omanar mv ein,w her eagluc os es olutionis infus ed.T he
plas ma N a + obtainedfr oms uc habloods ampleis low .
2.O v er br eathingis als oc alledhy per v entilation.O v er br eathingis fr equently c aus edby panic attac k s
( ie,hy per v entilationtetany ) .T hehighv entilationw as hes outtoomuc hc ar bondiox ide( C O 2 ) /c ar bonic
ac id,w her eby theC O 2 tens ionofthear ter ialblooddec r eas es s imultaneous ly w ithaninc r eas einits
pH .T his is analk alos is ( ar ter ialpH abov e7.45) .Alk alos is dis s oc iates pr oteins by mas s ac tionand
for mC a 2 + pr oteinate( F ig .17 9) .T hefallingex tr ac ellular c onc entr ationoffr eeC a 2 + ions r educ es
thethr es holdandopens N a + c hannels inneur ons ,mus c lec ells andmy oc ar dium.T her es ulting
r educ tioninmembr anepotentialinc r eas es theex c itability ofthetis s ues ,w hic hc aus es c ontinuous
mus c ular c ontr ac tions ( ie,tetanic c r amps ) .
Eq u at io n s
U n if o rm lyd ist rib u t ed su b st an cesindiluteds olutions behav elik egas molec ules at
atmos pher ic pr es s ur e( atm) .T heos motic pr es s ur ec anbeex pr es s edas :
Eq .1 1:P o s m o t =C R *T ,
w hic his theequiv alentoftheidealgas equation( P=n/V*R *T ) .C is thec onc entr ationofdis s olv ed
s olute.R is thegas c ons tant( =0.082latmmol 1 K 1 ) .
F ick' sf irst law o f d if f u sio n deals w iththediffus iv eflux per m 2 :
Eq .1 2:J d i f = D *dC /dx .
T hedimens ionofD is foundby dimens ionanaly s is oftheequationfor J d i f :
( J d i f moles s 1 m 2 ) =D ( dC /dx moles m 3 m 1 ) .
Ac c or dingly ,D has thedimens ion:m 2 s 1 .D is s mall,w henthemolec ules ar elar geandw henthe
s ur r oundingmediumis v is c ous .T heper meability c oeffic ient( ie,per meability ) for amembr aneis the
flux ( molm 2 s 1 ) div idedby thec onc entr ation( molm 3 ) for agiv ens ubs tanc eandhas theunitms
1.

Ein st ein ' srelat io n s tates thatthedis plac ements quar ed,( dx ) 2 ,is equalto2multipliedby D andby
thetime( t) elaps ed,s inc ethemolec ules tar tedtodiffus e:
Eq .1 3:( dx ) 2 =2*D *t.
T h eco rrect ed van ' t H o f f law :
Eq .1 4:=T R N /Vor =T R C
w her eR is theidealgas c ons tant( 0.082latmmol 1 K 1 or 8.31J ( Kmole) 1 ) ,andC is the
c onc entr ationgr adient.T his is thelaw for idealor ex tr emely dilutes olutions .

Am em b ran ep o t en t iald if f eren ceis c onv entionally definedas theintr ac ellular ( i ) minus the
ex tr ac ellular ( o ) elec tr ic alpotential.T heionac tiv ities ( c onc entr ations multipliedby theac tiv ity
c oeffic ient) ins idethec ellandouts idethec ellar eher ec alledC i andC o ,r es pec tiv ely .T heN er ns t
equationfor theequilibr iumpotentialofN a + ac r os s anion s elec tiv emembr aneat310Kr eads :
Eq .1 5: i o =( R T /z F ) ln( C o N a + /C i N a + ) Volts ( V)
V E q N a + =61.5log( C o N a + /C i N a + ) mV.
Intheequationabov eR is theidealgas c ons tant( 8.31J ( Kmole) 1 ) ,T is theabs olutetemper atur e,
z is v alenc eoftheionw iths ign( z =+1) ,andF is theF ar aday c ons tant( 96500c oulombs per
equiv alent) .T heac tiv ity c oeffic ientfor s odiumis 0.75andus edtoc onv er tc onc entr ationtoac tiv ity .
T h elaw o f rad io act ived ecay: IfN o is theinitialnumber ofuns tablenuc lei,thenumber ofnuc lei
r emainingafter atimet( N ) is giv enby :
Eq .1 6:N =N o *e k t .
w her ek is ac ons tantc har ac ter is tic ofeac hnuc leide,c alledthedis integr ationc ons tant.
Plasm a o sm o lalit yis c alc ulatedas follow s :
Eq .1 7:Plas ma os molality =( 2*N a + ) +gluc os e+ur ea
N or mally ,theplas ma N a + is 140mmolin1litr eofw ater ,andbothplas ma gluc os eandplas ma
ur eaar ear ound5mmolper lofw ater .T heplas ma os molality is giv eninmO s molper k gofw ater .
O nelofw ater is appr ox .equalto1k gofw ater .
T heMillm an eq u at io n .Ac onv enientv er s iontoc alc ulatether es tingmembr anepotential( R MP) at
body temper atur eis :
Eq .1 8:R MP=( g K + Eq K + +g N a + Eq N a + +g C l Eq C l ) /( g K + +g N a + +g C l )
T his equations how s thattheR MPis deter minedby thec onduc tanc e( g) ofthemembr anetoK + ,N a +
andC l ,andby their equilibr iumpotentials .

Selfassessment
Mu lt ip leC h o iceQ u est io n s
I.Each o f t h ef o llo w in g f ivest at em en t sh aveF alse/T ru eo p t io n s:
A.Pos itiv eions ( c ations ) diffus emor er apidly thr oughamembr anethannegativ eions ( anions ) .

B.T heN a + K + pumploc atedinthec ellmembr ane,is r es pons iblefor maintainingthehigh

intr ac ellular [K + ]andthelow intr ac ellular [N a + ].

C.T heper meability for N a + inc ellmembr anes is highc ompar edtothatofK + andC l .

D.Ins k eletalmus c lec ells ther es tingmembr anepotentialis 80mV,andtheequilibr iumpotential

ofN a + is +60mV.

Amembr anepotentialdiffer enc eis c onv entionally definedas theex tr ac ellular minus theintr ac ellular
elec tr ic alpotential.

II.Each o f t h ef o llo w in g f ivest at em en t sh aveF alse/T ru eo p t io n s:

A.T heloc al,s ubthr es holdr es pons eis gr adedac c or dingtothes timulus .

B.Ac c ommodationis apr ogr es s iv edec r eas einfir ingfr equenc y des pitemaintained
depolar iz ation.

C.Voltageinac tiv ationofN a + c hannels is inv olv edintheac c ommodationandinther efr ac tor y
per iods .

D.D ur ingtheear ly par toftheac tionpotentialthec ellmembr aneis r elativ ely r efr ac tor y .

Voltage gatedN a + ,K + andC a 2 + c hannels ar ec ompr is edofs ubunits w ithmembr anes panning
domains .

III.Each o f t h ef o llo w in g f ivest at em en t sh aveF alse/T ru eo p t io n s:

A.Saltator y c onduc tionis upto50times fas ter thanthec onduc tionthr oughthefas tes t
unmy elinatedax ons .

B.Saltator y c onduc tionoc c ur s bec aus ethec ellmembr anebeneaththemy elins heaths has a
highdens ity ofN a + c hannels .

C.Ats tandar dtemper atur e,pr es s ur e,dr y ( ST PD ) thev olumeoc c upiedby 1molofany idealgas
is 22.4l.

D.Eliminationw ithdec r eas ingr ateis ex ponential.

F ac ilitateddiffus ions how s s atur ationk inetic s ,andtak es plac ethr oughtr ans por tpr oteins notlink ed
tothemetabolic ener gy pr oc es s es .

Each o f t h ef o llo w in g f ivest at em en t sh aveF alse/T ru eo p t io n s:

A.O s molar ity is thenumber ofos motic ally ac tiv epar tic les ineac hlofs olution.

B.F ac ilitateddiffus iondoes nots how s atur ationk inetic s butmov es s olutes up hill.
Afamily ofhomologous c ar r ier pr oteins thatar ec odedby dis tinc tgenes mediates
fac ilitateddiffus ion.

C.G luc os e tr ans por t.T hetr ans por tpr oteins ( G LU T s ) s how amar k edtis s ue s pec ific ity w hic h
r eflec ts differ ingtr ans por tneeds ofv ar ious tis s ues .

D.T her elationbetw eenthepotentialdiffer enc emeas ur edw ithanion s elec tiv eelec tr odeandthe
ac tiv ity is giv enby theN er ns tequation.

E.T heD onnaneffec tis theex tr ac olloidos motic pr es s ur eofpr oteins olutions c aus edby unev en
dis tr ibutionofs mall,diffus iblec ations andanions .

T r y tos olv ethepr oblems befor elook ingupthean sw ers.

Highlights
T heidealgas law r elates thepr es s ur eP,thev olumeV,andthenumber ofmolofthegas n,andthe
Kelv intemper atur eT :( PV=nR T ) .
O nemolis theamountofagiv ens ubs tanc ec ontainingAv ogadr os number .T hev olume
oc c upiedby any idealgas is 22.4latST PD .
F ic k 's fir s tlaw ofdiffus ionr elates thediffus iv eflux per m 2 tothec onc entr ationgr adient.
T heD onnaneffec tofplas mais theex tr aos motic pr es s ur eofpr oteins olutions c aus edby
unev endis tr ibutionofs mall,per meablec ations andanions .
T hemembr anepotentialdiffer enc eis c onv entionally definedas theintr ac ellular minus the
ex tr ac ellular elec tr ic alpotential.
T heac tionpotentialis anall or noneelec tr ic als ignal,w hic happear s as apos itiv ew av ew hen
r ec or dinginter nally dur ingac tiv ity inaneur onor amus c lec ell.
Saltator y or leapingc onduc tionoc c ur s ,bec aus etheac tionpotentialis gener atedonly atthe
nodes .T hec ellmembr anebelow themy elins heaths has har dly any N a + c hannels andis
ther efor einex c itable.Saltator y c onduc tionis upto50times fas ter thanthec onduc tionthr ough
thefas tes tunmy elinatedax ons .
Inc as es w ithtoomuc hlipid,pr otein,gluc os e,ur ea,or alc oholinthebloodplas ma( ie
hy per lipidaemia,hy per pr oteinaemia,hy per gluc os aemia,ur aemia,andalc oholaemia) etc ,the
nor malplas ma N a + is r educ edby dilutionw iththeinc r eas ednon w ater fr ac tion.
O v er br eathingis c aus edby panic attac k s .T hehighv entilationw as hes outthec ar bondiox ide
( C O 2 ) /c ar bonic ac id,w her eby theC O 2 tens ionofthear ter ialblooddec r eas es s imultaneous ly
w ithaninc r eas einits pH .T his is analk alos is .Alk alos is dis s oc iates pr oteins andfor mC a 2 +
pr oteinate.T hefallingex tr ac ellular c onc entr ationoffr eeC a 2 + ions opens N a + c hannels in
neur ons ,mus c lec ells andmy oc ar dium.T her es ultingr educ tioninmembr anepotential
inc r eas es theex c itability ofthetis s ues ,w hic hc aus es c ontinuous mus c ular c ontr ac tions ( ie,
tetanic c r amps ) .
F u rt h erR ead in g
Br uc eAlber ts ,Alex ander J ohns on,J ulianLew is ,Mar tinR aff,KeithR ober ts ,Peter Walter ,Mo lecu lar

B io lo g yo f t h eC ell,F ifthEdition.G ar landSG ,2007.

Apps D K,BBC ohen,andC MSteel." Bioc hemis tr y ." Baillier eT indall,London,1994

Return to content
Return to chapter 1

Clickheretointroduceyourcommentsorcontributions