Cellular Physiology supplementary notes- Dr Bill Phillips
S U P P L E M E N T A R Y N O T ES F O R C E LL U L A R N E U R O P H Y SI O L O G Y D r W . D . Philli ps, D epa rt m e nt o f P hy siolo g y, U niv ersi ty o f Sy dn ey
Ele ct rica l pot en tia ls a n d th e el ec tro ch e mi ca l e q uilibri u m ac ro ss t he cell
m e m bra n e
Sig n alin g by n eu ro ns in v o lv es ch an g es in th e el ectri cal p ot en tials ac ross th ei r
me mb ran es
Sig n alin g by n eu r o ns in the n ervou s sy stem h as lo n g b een k no wn to in v o lv e
elect ric al p o ten tials (vo lt ag e di ff ere n c es) w hich co uld b e me asu r ed , fo r exa mple ,
b y p lacing el ectr od es o n th e su r fa ce o f t he sku ll ( E E G ) . Wh en phy sio log ists
d ev elop ed tech niq u es fo r p la cing tin y elect r od es in sid e neu ron s (in th e 1 9 40 s an d
5 0 s) th ey we re ab l e to me asu r e ele ct rical p ote ntial di ffe re n ces a cro ss th e plas m a
me mb ran e o f the c ell an d to sh o w th at sig n alin g by n eu ro ns inv o lv ed tr an sien t
ch an g es in the v alu e o f th is m e m b ra ne po te ntial . In a he althy n eu ro n th at is n ot
in th e p ro cess o f sig n alin g (r estin g) , the in sid e of th e c ell (the cy to p l asm ) is mor e
n eg ativ e th a n the o u tsid e o f th e c ell (ex tr a cellu la r) an d th is resti ng me m b ra ne
po t en tia l is th u s ab o u t -6 5 millivo lts ( m V ) or -0 .0 65 v olts. A ll typ es o f h ealth y
cells h av e a m em b ra ne p o ten ti al.
Th e lip id me mb r an e o f th e n eu ro n s ep a rat es diffe ren t co n c en tratio n s o f io n s
Th e p l asm a m e mb r ane co n sists o f a li pid bil a yer . Th e p hosp holipids th at m ak e up
this b ilay er h av e on e h y d ro p h ilic end (a ch a r ged o r p ol ar g ro u p su ch as a p h osp h ate
g ro u p ) and a h y d ro p h o b i c (u n ch arg ed , no n -p o lar) t ail. Lipid s o f this type t end to
sp o n taneou sly fo r m in to a lipi d bilay er w hich is a lo we r en erg y stat e fo r th e m
b ec au se th e hy dr op ho bic ta ils can in t er act with ea ch o the r and th e hy d rop hilic
hea d g ro u ps can in t er act with wat er mol ecu les ( wh i ch a re h igh ly p o la r) o n eith er
sid e. L arg e nu mbe rs o f int rinsi c (in teg ral) me m b ra ne p rot ei ns float within the
lip id b ilay e r. Th ey sp an th e bilaye r with t h eir h yd ro pho b i c amin o a cid r esidu es
sp an n ing th e hy d rop ho b ic co r e of th e m e mb r an e . Mo lec u les o r io n s th at ar e ch arg ed
o r p o l ar (su ch as io ns) c an n ot easily p as s thro u g h th e b ilay er b ec au s e o f its
h y d ro p h o b ic cent re .
To try to ex p l ain the ele ctri cal p otenti al across the me mb ran e p h ysio log ists
ex a min ed th e con centr atio n s o f io ns o n eith er sid e of th e m emb ran e . Th ey fo un d
that in side th e p l as ma me mb ran e the con c e ntratio n s o f po ta ssiu m io ns (K + ) and
o rg a ni c a nio ns ( A - ) w er e mu ch h igh er tha n in th e ex tra cellu l ar fluid wh il e th e
co n c en tr atio n s of so di u m io ns ( Na + ) an d c hl orid e ions ( Cl - ) w e re mu ch lo we r th a n
o u tsid e. Th ese ar e th e ty p es o f ion s th at are mo st i mpo rt ant in sig nalin g alon g
n eu ro n s .
Distrib u tio n o f m ajo r io n s ac ro ss th e m e mbr a n e o f th e s quid gi an t ax o n
Io n
Cy to pla s m
(mM)
Ex t rac ellula r
(mM)
K+
400
20
+
Na
50
44 0
Cl 52
56 0
A385
* th e me mb ran e p o te n tial at wh i ch th e re is
acr oss th e m emb ran e .
N er nst
po t en tial*
( m V)
-75
+5 5
-60
n o n et mov em en t o f th e io n in qu estio n
Ele ct roc he m ica l e quili bri u m
Th er e ar e t w o fo rc es wo r ki ng o n eve ry io n . Th e fi rst is a ch e mic al for ce du e to
the co n ce nt ra tio n g ra die nt; en erg y is req uired to co nc en tr ate su b stan ces a n d
55
Supplementary Notes on Cellular Neurophysiology- Dr Bill Phillips
wh er e a co n cent ratio n g r ad ient exists, io ns, lik e no n- cha rg ed mo l ecul es , will
d iffu se d o w n th e gr ad ie n t to w ar d s th e r eg io n o f lo wer co nc en tr ation (ie . th e re is a
'ch emi cal ' fo rc e w an ting to mo v e th e m a cros s the me mb ran e: so d iu m into th e cell ,
p o tassiu m o u t o f the c ell etc .) . Th e s eco n d fo rc e a ctin g on ev ery io n is th e
elec tro s ta ti c fo r ce d u e to its ele ctric al ch arg e.
Po r e- fo r min g p ro t eins in th e n euron me mb ra ne sele ctively allo w pa rticu l ar typ es o f
ion s to p ass th rou gh
Th e fo r ces acting o n io n s wo uld h av e no ef fect if ion s co u ld n 't p ass th ro ug h th e
me mb ran e, b u t so diu m , p o t assium and chlo ri de ion s c an mo v e ac ro ss the m em b ra n e
thro u g h po res in th e me mb r an e. Thes e po re s are fo rm ed b y ion c ha nn el pr o t eins .
Th e stru ctu re o f th es e io n ch an n els is su ch th at th ey are sel ective f or p a rticula r
typ es of io n s ac co rd ing to th e siz e , sh ape and ch arg e p r op e rties th e io n s . Th e
n eg ativ ely ch a rged o rgan i c io n s ( A - ; these i n clud e ne g ativ ely cha rg ed c y top las mic
p ro tein s an d mol ecu l es such as A T P) c an no t p ass th ro ug h th e me mb ran e at all,
me an in g th at th er e is a p e rm an ent c on c entratio n g r adient o f A - ac ross th e
me mb ran e. On the o th er h an d th e n eur o n me mb ran e is b eliev ed to co n tain io n
ch an n els s electiv e for th e p ositiv ely cha rg ed io ns ( catio n s ), Na + an d K + an d oth e rs
selectiv e for th e n eg ativ ely ch arg ed ion ( a nio n), Cl - , th at ar e o p en all th e ti me
allo wing ea ch of th es e io n s to move in o r ou t of the me mb r an e ac co rd in g to th e
fo rc es work in g on th e m .
El ectro ch emi cal equ ilib riu m fo r p otassiu m io n s
It is e asiest to u n d erst an d h o w me mb ran e p otentials ar e g en e rate d b y co nsid ering
the fo r ces wo rk in g o n e ach io n o n e at a ti me . T he el ect rostatic fo r ce can wo rk fo r
o r again st th e c o nc en tr atio n g rad i en t of the io n in q u estio n . For ex amp l e K + is
mo r e co n c en tr ated insid e th e c ell than ou tsid e, so the p ri ma ry ch e mic al fo r ce w ill
atte mp t to mo v e K + th rou gh me mb ran e ch a n n els and o ut o f th e c ell b u t at th e
me mb ran e po tential o f th e r estin g neu ron (ab o u t -65 m V ) th e ion must wo rk ag ainst
the attra ction o f the n et n e gative cha rg e in si de the cell an d th e rep ulsion d u e to th e
n et p o sitiv e ch arg e o u tside th e cell . I f th e r e w as o nly K + ac ro ss th e me mb ran e to
co n sid e r, th en K + w o u ld flo w o ut o f th e cell an d th e sh ift o f cha rge o ut o f th e cell
wo u ld in cr eas e th e o p po sin g ele ctric al d riv in g for ce . Fin ally , th e in wa rd elect ric al
d riv in g fo r ce wo u ld exa ctly equ al th e o utw ard che mic al fo rc e d ue to th e
co n c en tr atio n g r adien t an d th er e wo u ld b e n o n et fo r ce on th e K + io n a n d thu s n o
n et mo v em en t (or flux ) . This situ atio n is illustrated in Fig 1 belo w . The me mb r an e
p o ten tial at whic h th is eq u ilibriu m o ccu rs is called th e N er nst p ot en tial for
p o tassiu m ( E K ) . E K is ty pic ally abo u t -75 m V .
56
Cellular Physiology supplementary notes- Dr Bill Phillips
Fig 1 .
Nernst potential for K+
Resting potential
K+
Net outward movement
of potassium
K+
No net movement of
potassium
Extracellular
""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""" !!!!!!!!!!!!!!!
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
"""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""
Intracellular
Electrical driving
force
Chemical driving
force
Electrical driving
force
Chemical driving
force
-75mV
-65mV
E ach o f th e ion s th at is d istribu ted in a g ra dien t ac ross th e m emb ra n e h as its o wn
N ern st p oten ti al (s ee tab l e) an d th e N ern st p o tential can b e c alcul ated a cco rd in g to
the fo r mula (st ated h e re fo r th e c ase o f po t as siu m):
E K = R T ln [ K + ] o
Ne r nst e qua tio n fo r K +
zF
[ K+] i
Wh er e E K is th e v alue o f me mb ran e po tenti al fo r w h ich K + is in equ ilibriu m ( th e
K + Ne rns t po te ntial ), R is the g as co nst an t, T is temp er atur e in d eg re es Kelvin , z
is th e v alan c e of th e io n (in th e cas e o f p otassiu m it is +1) , F is the F ar ad ay
co n stant . Th e r em ain d e r o f th e equation is th e n atu ral lo g arith m (b ase e) of th e
ratio o f [ K + ] o o v e r [ K + ] i (th e co n ce n tration s of K + on the o u tsid e a n d inside o f th e
cell resp ectiv ely) .
[I t is i m p o r ta n t to n o te th o u g h th a t th e io n g ra d i en ts d o n o t ru n d o wn d u r in g th e
fu n c t io n in g o f h ea lth y n eu ro n s a s th e ra t e o f io n f lo w is sm a l l co m p a r ed to th e
co n c en tra t io n d i ff e ren ce s a n d th er e a re tra n sp o rt e r p ro t e in s ( p u m p s ) th a t wo rk to
m a in ta in th e g ra d i en ts ] .
Io n m o v e m e nt ac ro ss t he m e m bra ne g en era tes ele ct rica l po t en tial
In th e r estin g n e u ro n Na + , K + a n d Cl - a re con tin ually mo v i ng thr o ugh th e
me mb ran e a cco rd in g to th e b alan ce o f fo rc e s actin g on e ach o f th em . Sinc e ion s
are c h a rged , th ey ca rry a cro ss th e me mb ra n e ele ctri c c ur re nt . Th ese el ectri c
cu rr en ts g en er ate an el ectri cal po tenti al d iffe ren ce and th e su m o f th ese mo ve m ents
o f ch a rg e is respo nsib le fo r g ene ratin g the m emb ran e po tential o f th e cell .
Th e r esti ng m e m b ran e po te ntia l an d t he si gnific a n ce o f io n pe r m ea bili ty
So d iu m, p o tassiu m an d ch lo rid e ions e ach hav e th er e o w n N ern st p o ten ti als (s ee
tab le) b ut the r estin g m e mbr an e p ot en tial is d iffe ren t f ro m ea ch of th e m .
Co n seq u en tly K + , Na + a n d Cl - c ur re nts are co nstan tly flo win g a cross th e
me mb ran e o f the restin g n eu ro n an d e ach o f th ese curr en ts ten d s to pu ll th e
me mb ran e po tenti al to w ard s th e r esp e ctiv e N ern st p ot en tial o f th e io n in q uestion .
Ho w ev er , th e a bility of ea c h ion to in flu e nc e th e me m b ra n e po te ntial d e pe nds
upo n i ts a bility t o pa ss t hro ug h t h e m e m bra ne , w hich in turn is th e p ro duct o f
57
Supplementary Notes on Cellular Neurophysiology- Dr Bill Phillips
the nu m b er o f ion c ha n n els throu gh wh i c h it c an p ass an d th e con d uc ta n ce of
tho se ch an nels (i e. th e to tal co nd uct an c e o f th e m emb ran e fo r th at io n per a re a o f
me mb ran e) . Co nd uc ta nc e (sy m bol g) is ju st th e m easu re o f th e ab ility of c urr en t to
p ass a cro ss th e resist an t m e mb r an e fo r an y g iv en for ce/po t ential d if fe ren ce .
Co n d u ctan ce is me asur ed in Sei men s (o fte n ex press ed as µ S/c m 2 o f me mb ran e
are a) . In the restin g neu ro n the tot al co n du ctanc e fo r K + (n u mb e r of ch an n els x
ind iv id u al ch ann el con d u ctan ce/ c m 2 ) is a bo ut 2 0 fo ld g re ate r than th e to t al
co n d u ct an c e fo r N a + . Th u s in th e restin g ne u ron , pot assiu m is the d o mina nt ca tio n
(p o sitiv ely ch arg ed io n ) an d th e res tin g m e mb ra ne pot en tial is abo ut -65 m V,
clo ser to th e N ern st p o ten tial f or K + ( E K =-75 m V) th an th at fo r N a + ( E N a = +55 m V) .
Th e m e mb r an e p o t en tial is th us det er min ed b y th e mo v e ment o f io n s a cro ss th e
me mb ran e th ro u g h io n -sel ectiv e chann els. T h is results in a n et n eg ativ e ch a rge o n
the in sid e o f th e c ell rel ativ e to th e o u tsid e ( the o utsid e of th e cell is, b y definitio n
zero p o ten tia l) . Th e mov e m en t o f th e ion s do w n their resp ectiv e con ce ntration
g rad ie nts (tra ns m e m br an e cu rr e nt) thu s con tribu tes to th e restin g me mb ran e
p o ten tial o f the c ell.
At th e r estin g me mb r an e p o ten ti al o f th e n euro n , th e in side o f th e n euro n is
n eg ativ e (s ay -6 5 m V) b e ca u se it con t ain s m o re u n bal anc ed n eg ativ e ch a rges th an
the o u tsid e ( wh ich is d efin ed as 0 m V) .
If th e in side b ec a me less neg ativ e
co mp ar ed with th e o utsid e, w e wo uld s ay th e me mb r an e was b eco min g de po la ris ed .
If th e in sid e be co mes mo r e n eg ativ e, w e s ay it is hy p er pola rise d.
A ctiv e tra ns po r t o f so di u m a n d po ta ssiu m i o ns a cr oss th e m e m b ran e
If th e n eu ron d id n o t act to co r re ct fo r it, t h e co n cen t ratio n g radi en ts o f s o d ium ,
p o tassiu m an d ch lo rid e io n s w o u ld b e ex p e cted to ru n do wn e v en tu ally and as a
resu lt th e m em b ra n e wo u ld b e co m e depo l a rised . Ind eed if th e d ru g o u a b ain is
ap p lied to n eu ron s th e me mb r an e p o tential do es slo wly de p o laris e an d it w as this
o b serv atio n that allo w ed th e id en tific ation of th e Na + / K + - pu m p . Th e Na + / K + -p u mp
is a co mp l ex o f p ro tein s in th e c ell me mb r an e th at h y d ro ly s es A T P an d uses th e
en e rg y o f th e h y d ro lysis to p u mp potassiu m in to th e c ell ag ainst its co n cen t ration
g rad ie nt. Fo r e ac h t wo po tassiu m ions pu m p ed in, th e sa me p rotein p u mps th r ee
so d ium io n s ou t o f th e c ell ( against th e sod iu m co n c en tr atio n g r ad ien t ). Sin c e it
h y d ro lyses A T P to prov id e the en erg y to co ncentr ate N a + outsid e the cell an d K +
insid e, th e N a + / K + -p u mp is also re fer red to as the N a + / K + - A T Pas e and is an
ex a mp le o f pri m a ry a c tive t ra nspo rt .
Wh en th e N a + / K + - p u mp is o p er ating in a neu ron , it is the pump th at sets an d
main t ain s the r estin g p o ten ti al of th e cell . Thu s th e Na + / K + -pu mp com p ens ates fo r
the rev ers e mov em ent of so d iu m and p otassiu m ion s th ro u gh th e io n ch an n els .
Th us th e ess ential f eatu res in dete rmin in g th e me mbr an e p o t en tial ar e; th e
co n c en tr atio n g radi en ts o f ea ch o f th e io n s , th e activ ity o f th e N a + - K + - pu mp in
main t ain in g th o se g ra dien ts in th e lo ng ter m and th e me mb r an e co n d uct anc es fo r
ea ch of th e io n s . In a r estin g n eu ron the co nd u ctan ce fo r K + (g K ) is s m all, b ut the
co n d u ct an c es fo r th e oth er io n s a re ev en s m aller so at thes e ti mes th e K + cur rent
(I K ) is th e d omin an t cu rr en t in d et er mining t h e m e mb r ane p otential . As a r esult o f
this th e r estin g me mb ran e p o tential is close t o th e N ern st po tenti al fo r K + .
Pa ssiv e ele ct rica l p ro pe rties o f ne ur o ns
El ectri cal sig n aling in n eu ro ns in volv es io ni c cur rents b eing s wit ched o n an d o f f in
o n e p art o f th e n euron m e mb r ane and the res ultant p o ten ti al d if fe ren ce sp r ead in g to
o th er p arts o f th e n eu ro n me mb ran e v ia lo c al circ uit cu rr e nts . Fo r ex a mple , in
the moto r n eu ro n , wh en ex cita t o ry syna pses o n th e d endrit es ar e activ ated ,
58
Cellular Physiology supplementary notes- Dr Bill Phillips
d ep o la risin g io n ic cu rre n ts s witch on in th e me mb ran e u n d er th e syn apse .
El ectri cal cu rr ent r esu ltin g fro m this will sp rea d a cross the me mb r an e of th e moto r
n eu ro n in a w ay th at is d et er min ed b y th e p a ssive m e m bra n e pro pe rti es (o r c ab le
p ro p e rties) o f the cell . Und ersta ndin g h o w transien t p o ten ti als mo v e in ti me an d
sp ac e is imp o rt an t bec au se in th e n eur o n cell b o dy sm all d epo la risation s
o rig in ating fro m sy n ap s es all ov er th e ne u ro n me mb r an e ad d tog eth er in a p ro cess
called su m ma tion at th e t rig ge r zo n e o f th e n eu ro n (th e me mb r an e of th e a x o n
h illo ck ). Th e su m of th es e sm all dep ol arisa tio ns at th e trig ge r zon e at an y g iv en
instan t d eter min es w h eth er th e n eu ro n will fire an action p oten ti al o r n o t. This
p ro c ess is k n o wn as sy na pti c i nt egra tion . Actio n po tenti als o nly fir e w hen th e
me mb ran e p o t ential rais es h ig h enou g h to o p en a c ritic al n u mb e r o f th e vo l tag e g a te d so di u m io n ch an nels in th e me mb ra ne, Passiv e m em b r an e pro perti es also
ex p lain h o w , o n ce an action p ot ential is initi ated , it c an pro p ag at e ( mo v e along ) a n
ax o n .
Th e elect ric al pr o p e rties o f th e ax on (o r a th in d end rit e) c an b e co mp ar ed to an
insu lated su b m arin e tel eg r ap h wi re an d th at is wh e re th e math e mati cal equ ation s
that ex p lain th e p assiv e sp r ead o f me mb r an e potential alo ng an ax on o riginated .
So me p ro p e rties o f th e n eu ron m e mbr an e d o n't ch an ge d urin g th e co u rse o f
elect ric al sign aling .
Th e i mp o rtan t ele men ts of thes e pa ssiv e m e m bra n e
pro pe rti es ar e:
1.
2.
h o ld
3.
co n d uct a n ce o f v olt a g e -ins ensi tiv e c ha nn el s (le ak ag e ch an n els)
(th e n o n -g ated io n ch an nels r ef er red to ab ov e that a re al w ay s op en )
m e m bra n e ca pa cita nc e (th e ability of th e p lasm a m emb ra ne to b u ild u p an d
ch a rg e , lik e a n ele ctric al cap acito r)
co n d uct a n ce o f th e cy topla s m (this is part icu larly signi fican t in the cas e
o f a lo n g th in tu b e o f me mb ran e lik e th e ax o n o r d en drite of a n eu ron )
E ach of th ese p ro p erti es a ff ects th e sp re a d o f ch an g es in m e mb r ane p oten tial
(sig n a ls) d o w n th e ax o n . Co nsid er wh at ha p pen s wh en a mi cro ele ctro d e is p u sh e d
thro u g h th e p las ma me mb r an e of the axon a nd a cu rr en t is in jected in to th e c ell to
cau s e th e me mb r an e su r ro u n din g th e ele ctro de to b e d epo la rised . Th e lo cal
p o ten tial ch ang e at th e site o f th e el ectro d e is called th e el ec tro to ni c po te ntial o r
local res po ns e .
Th e cu rre n t then sp re ads o u t alon g th e insid e o f th e axo n (th e axop las m ). As it d oes
so th e c u rr en t is dissip ated in t w o w ays. P art o f the cu r ren t w ill in itially c an c el
o u t th e n eg ativ e ch arg e o n th e in sid e o f th e me mb r an e . W e say it discha rg es th e
m e m bra n e ca paci ta n ce . Cap acit anc e is a p h ysical p ro perty o f th e lip id b ila yer .
Cap acito rs a re d ev i ces wi d ely u s ed in th e ele ctro ni cs in d ustry . W hen eve r t wo
elect ric al co n d u cto rs a re s ep a rat ed b y a th i n in su lator ther e will b e a m easu rabl e
cap acitan ce p ro pe rty . C h a rg e will ten d to acc u mulat e o n eith er sid e o f th e insu lato r
b ec au se o f ele ctro st atic attra ctio n to an ex c e ss o f o p po site c h ar g e on th e o ther sid e.
Th e th in n er th e in su lato r, the stro n ge r the cap acit an c e pro p e rty (p e r sq u a re
cen ti met re) . Th is is b e cau s e elect rostati c attraction d e clin es with th e sq u ar e o f th e
d istan ce o f sep ar atio n. Cap acito rs ar e u sef u l in electron i cs b e cau s e th ey stor e
ch a rg e and ch ang e th e r ate th at ele ctri cal po ten tials ch ang e in resp o n s e to c u rr en t
ch an g es. The sa me is tru e in n euron s . I n the cas e of th e cell , th e lip id b ilaye r is th e
insu lato r wh ile th e t wo c o n d u cto rs a re the s a lty w ater o f th e extr ac ellu lar flu id an d
the salty wat er o f th e cy to p l asm . Th e ch a r g e will b e in th e fo rm o f io ns. This
me an s th at as tr ans me mbr an e cu rr ents start t o flo w th ey t ake ex tr a ti me to alter th e
me mb ran e p o tenti al b ec au se th ey mu st eith er d isch arg e th e n eg ativ e ‘c ap a citan ce
ch a rg e ’ (d u ring d ep o la risiatio n ) or r ech arg e it (d u rin g r ep o la risatio n ). M e mb r an e
cap acitan ce c an b e r ep r esen t ed b y th e sy mb o l of a cap acito r (t w o co n du ctive p lates
59
Supplementary Notes on Cellular Neurophysiology- Dr Bill Phillips
sep a rate d by a n on- co n d u ctive g ap ) in an ele ctric al ci rcu it th at r ep r esents th e
p assiv e p ro p erti es o f th e m e mb r an e ( Fig. 2 ).
Alth o u g h th e lip id b ila y er p ro v ides a th in n o n - con ductiv e g ap th at allo ws th e
me mb ran e to a ct as a c ap a citor , it also con tains so m e co n d uct an c e el em ents , th e
v o ltag e-in s ensitive io n ch an nels (no n- ga t ed ion lea ka g e c han n els) . Th e re m ain d e r
o f th e cu rr en t will th us le ak ou t o f the axo n thro u gh thes e ch an n els (th e restin g
m e m bra n e con d uc tan ce ) co mpleting a cir c uit b ack to th e p o int at wh i ch cur rent
w as in ject ed . Th e ch an n els a re f ar f ro m p e rfe ct, r elativ ely fe w ion s c an pass per
seco n d , so th e me mb ran e co n d uct anc e is ind icated in o u r eq u iv alen t cir cu it b y th e
sy mb o l fo r a r esisto r . Th e co n du cta n ce (g ) o f a n ar ea o f m e m b ra ne is si m ply th e
inv e rse o f its r esista nc e (r , m ea sur ed a s O h ms- sy mb ol Ω ) .
Membrane has
electrical capacitance
Ion channels in the
membrane have resistance
++++
-------The axoplasm is narrow
and has resistance
El ectrica l c o mp o n en ts o f th e a x o n tha t affe ct th e sp rea d o f a ctio n po ten tia l sig n als .
E ach sh o rt s egm en t o f th e ax o n len gth can t hu s b e th ou gh t of as th e eq u iv alen t o f a
resisto r an d cap acito r co nn e cted in pa rallel a cro ss wh ich a cu r ren t is ap plied .
Th e in je cted in wa rd cu r ren t w ill b egin to disch arg e the cap a citiv e char g e o n
m e mb ra n e. Th e n ec essity of d isch arg ing o f the plasm a m e mb r ane slo ws d o wn th e
sp re ad o f d ep o la risation d o wn th e ax o n o r d en d rite . So m e a x on s h av e a r elativ ely
g re ater cap acity to sto re ch a rge th an oth e rs , in su ch ax on s (p arti cu larly in s m all
d iam ete r ax o ns) , th e a ctio n p o ten tial p rop ag a tes mo r e slo w ly.
Fig 2 .
Inject test pulse of current
Extracellular fluid
Axon Equivalent circuit
+
Axoplasm
Vm
60
Changes in Vm seen at different
positions along the axon
Cellular Physiology supplementary notes- Dr Bill Phillips
Pa ssi ve el ectri ca l p ro perti es d eter mi n e th e r ate of p ro p a ga tio n o f action p o ten tials
in a n ax on . Th e fig ur e a b o ve sh o ws the lipi d b ila yer sepa r a tin g th e e xtra c ellula r
flu id fro m th e c ytosol/a x o p la s m ( ele ctrica l c o n du cto rs se pa ra ted b y an in sula to r ).
El ectrica l co mp o n en ts co mp l ete th e equiva l e n t circu it th ro u g h whi ch dep o la risin g
cu rrent flo ws a lo n g th e a xo p la s m , an d the r e tu rn cu rren t in the e xtra c ellu lar fluid .
Th e p a ssi ve ele ctrica l p ro p erties mo d if y th e resp o n s e o f th e m e mb ra n e p ot entia l
( V m ) to a b rief in wa rd cu rr ent a t ea ch po i n t alo ng th e a xon a s ind icat ed b y th e
tra n sien t me m b ra ne p oten tia l tra ces ( V m ) a t the b otto m of th e fig ure . Wh ether the
b rief d ep o la risin g in wa rd cu rren t is gen er ated a rtificially by the sti mu lator a s
sh o wn , o r n a tu ra lly b y th e o p enin g of volta g e-ga te d Na + ch an nels ( Ho dg kin C ycl e) ,
the p a ssi ve p ro p erties d i min ish th e sp r ead of ch an g es in th e V m in the sa m e wa y.
As th e in j ect ed cu r ren t mo v es alon g th e in side o f th e ax on it d isch arg es th e
me mb ran e cap acit an c e and lea k s o u t th roug h the me mbr an e co n du ct an c e. In do in g
so it gen er ates ch an ges in th e m e mbr ane p ot en tial. Th e ax o n is v e ry thin an d thu s
h as mu c h mo r e resist anc e to the spr ead o f c urre nt th an the e x tra cellu l ar fluid s o it
is n e cess ary to co n sid e r th e a x o plas m ic r esis tan ce .
Ax o p l as mic resistan ce m ean s th at the a mo u n t o f cu rre n t flo wing fro m th e el ectro d e
to th e site whe re m e mb r an e p oten ti al ( V m) is measu red ( an d th er efo re th e ch ang e
in m emb ran e p o t ential it p ro d u ces ) d e clin es as w e mo ve alon g th e axo n a wa y f ro m
the el ect ro de . Th e ax op las mi c r esistan ce is sh o wn b et we en ea ch m e mbr an e cir cu it
u n it in the equ iv alen t cir cu it ab o v e ( Fig 2) . Th e r elatively hig h resist anc e (lo w
co n d u ct an c e) o f th e ax o p l as m le ad s to a d e cl in e in the a mp litud e o f th e sig nal with
d istan ce alo ng th e ax o n , wh ile m em b ra ne c on du ctan ce dissip ates th e lo cal cir cu it
cu rr en ts an d li mits th e d istan ce th at chan g es in th e m e mbr an e p o ten tial (Δ V m ) can
p assiv ely spr ead b e fo r e th ey d i minish to n oth in g.
Th e p assiv e sp r ead o f m e mb r ane d ep ol aris atio ns (or h y pe rp ola risatio ns) sub je ct
o n ly to th e eff ects o f me mb ran e co n d uctan ce , m e mb r ane c ap a citan ce an d
ax o p las mic resist an c e is k n o w n as ele ct ro to nic con d uc tio n (eg . a s mall amplitu d e
me mb ran e po ten ti al ch an g e du e to a sy n ap tic curr en t o r in j ectio n o f cur rent th ro u gh
a mi cro ele ctro d e) . Su ch cu rr ents f all off in amplitu d e exp o n en tially with dist anc e
fro m th eir so ur ce .
Th e a c tion p ote n tia l
El ectro to n ic co nd uctio n is n o so lutio n to th e n e ed to s end el ect ric al sig n als alon g
ax o n s th at m ay be u p to 1 metre in leng th . T h e so lutio n th at ev o lved was the a ctio n
p o ten tial, a sel f-r eg en e ratin g sig n al th at is g ene rat ed and m ain tain ed b y th e
seq u en ti al o p en in g o f v o ltag e-se n sitiv e io n chan n els sele ctive for (1) sodiu m an d
(2 )p o tassiu m .
If th e m em br an e o f th e n eu ro n is d ep olaris e d sufficien tly (to thresho ld ) an actio n
p o ten tial is trig ge red .
Th e d epo la risati on c au ses vo lta g e-s ensi tiv e so di u m
cha n nels in th e me mb ran e to op en an d so d ium ion s ente r the c ell m u ch mo re
rapid ly th an wh en at rest . Th e sod ium io ns car ry with them el ect ric al ch a rg e
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Supplementary Notes on Cellular Neurophysiology- Dr Bill Phillips
(cur ren t ) and cau s e th e m emb ra n e to be co m e ev en mo re d ep ola rised . Th is a d ded
d ep o la risatio n op en s ev en mo re voltag e-s e n sitiv e sod ium ch a n n els , cau sing th e
me mb ran e to b eco me ev en mo r e d epo la rised . This self- rein for cin g proc ess ensu res
that th e m e mb r an e p o te n tial rap idly rises f ro m th e n eg ativ e r estin g p o tential to
ap p ro ach th e N ern st p o ten ti al for sod iu m (sa y +5 5 m V) .
Ho w ev er , th e N a + -d riv en me mb ran e d epo la ris atio n do es no t p ersist fo r t w o r eas o n s:
(1 ) d epo l aris atio n ev e n tually c auses th e op en v oltag e -sen sitiv e so dium chan n els
slo wly b eco m e in a ctiva t ed (s wit ch o f f) o f t h eir o wn ac co rd an d pass n o mo re N a +
cu rr en t; (2 ) th e dep o laris atio n also o p en s vo lta ge -se nsitiv e po tassiu m c ha n n els
that th at h av e a mu ch h ig h er con du ctan c e fo r p o tassiu m ion s than the vo ltag einsen sitive ch an n els (th e n o n -g ated ch an nels resp on sibl e fo r the restin g V m ). T h e
v o ltag e-s en sitiv e K + - ch an n els a re o f th e so called delay e d re cti fie r typ e m ea n in g
that th ey o p en mo re slo wly th an the v oltag e-se n sitiv e so diu m ch an nels aft er th e
me mb ran e is first d ep o la rised . Th e r esult o f th is d elay is th at th e flo w o f K + ou t of
the cell o ccu rs on ly a fte r th e d ep o la risatio n du e to Na + in flo w h as raised th e V m u p
to abo u t +50 m V an d th is is abo ut th e sa m e time that th e in w ard N a + cu rr en t is
b eing sh u t o ff d u e to th e d el ay ed in activ atio n o f th e v o ltag e-s en sitiv e so diu m
ch an n els. W ith th e N a + cu r ren t o ut of t he p ictu r e , the out w ard K + cur rent
repo la rises th e me mb ran e. Se e Fig . 3 .
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Cellular Physiology supplementary notes- Dr Bill Phillips
Fig . 3 Co n d u ctan ce ch an g es con tribu ting to t h e action poten ti al
Membrane potential
sodium conductance
potassium conductance
0
1
2
Time (msec)
3
Th us , th e o p eni ng o f vo l ta ge -se nsitiv e sodi u m c han n els c au s es th e sel frein fo rcing d ep ola risatio n ( N a + c urr en t flo w s in), th en ( d ela y ed ) ina c tiv atio n o f
the sod iu m c o nd uct an c e an d th e ( delay e d) op eni ng o f t he po ta ssi u m cha n nel
co n d u ct an c e resto res the n eg ativ e m emb ran e p o ten tial.
Ch a n g es in co nd u cta n c e l ea d to ch a nges i n curr ent which a lter th e me m b ran e
p o ten tia l cau sin g fu rth er ch an g es in io n ch an n el co n du ctan c es.
Im m ed iately aft er th e actio n p ote n tial ther e is a brief p eriod wh en it is imp ossib le
to trig ger a s ec on d a ctio n p o t ential . This is called the a bso l ut e r ef ra c to ry p erio d
an d it is d u e to th e fact th at th e v oltag e-g ate d sod ium ch an nels r e main in a ctiv a te d
an d u nable to o p en f o r a short tim e f o llowing the action p oten ti al.
The
a fte r pot en tia l (a h y p erp o laris atio n) th at fo l lows th e action p ot en tial is d u e to the
b elated clo sin g o f so m e of th e vo lt a g e-g ated po t assiu m ch ann els. T h is
afte rp o ten ti al is respo nsib l e fo r th e so call e d relativ e r efr a ct ory pe riod (o r mor e
p re cisely , t he pe rio d of re d uc ed ex ci tab ility) o f s eve ral millise co nd s d u ring
wh i ch mo re depo l arisin g cu rr en t than no r m al is requ ired to re ach thr esho ld fo r
firin g of a se co nd a ction p o t en tial .
Th e u n iq u e fe atu r e of th e a ctio n po t ential is the f act that it is all-o r- no n e . O nc e a
thresh o ld is re ach ed wh er e the n et in wa rd c u rre n t (flo w o f p ositiv e ion s) ex c ee d s
the n et o u t w ard cur ren t , th e v oltag e sensitiv ity of th e io n ch an n el ga t e me ans that
mo r e an d mo r e so dium ch ann els will o pen an d the me mb ran e will b eco m e mo re an d
mo r e d ep o la rised . T h e v o lt ag e d ep en den t gating and d el ay ed in a ctiv atio n o f th e
so d ium cu rr ent ar e du e to stru ctu ral f eatu res o f th e ch an n el p ro tein . Si mila rly th e
d elay ed op en in g o f th e p o tassiu m co n du ct an ce is a un iq ue fe atur e of th e structu re
o f th e d el ay ed r ectifi er ty p e of p otassiu m ch a n n el p ro tein . A field o f in t ense
inv estig atio n b y ph ysio lo g ists an d mol ecu l a r b io lo gists co n c ern s th e q u estio n o f
h o w st ru ctu ral f eatu res o f th e pa rticula r ch ann el p roteins mig ht exp l ain th eir
ch a ra cteristi c ty p es o f g atin g .
Th e d eclin e in co n c en tr atio n gradi en ts o f s o d ium and po tassiu m io n s th at mig h t
o th er wis e fo llo w a lon g seri es (a tra in or vol ley) o f actio n po tenti als is avo id ed by
the a ctiv ity o f th e Na + - K + - A T Pase (th e sodiu m/po ta ssiu m pu mp ). Ple ase r em e mb e r,
the ra p id (f ew millis eco n d s ) rep o larisatio n ph a se o f th e a ction p o te n tial is ca u se d
b y th e a ctiva tio n of th e vo ltag e g a ted pota ssi u m ch a nn els. Th e p u mp is to o w a y to o
slo w a ctin g to ca u se suc h fa st ch a ng es in m e mbran e po ten tia l .
Ele ct roto nic co n du ctio n a n d t he sp re ad o f actio n pot e ntia ls
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Supplementary Notes on Cellular Neurophysiology- Dr Bill Phillips
El ectro to n ic co nd u ctio n (d iscu ss ed p re vio u s ly ) is imp o rtan t be caus e it d eter mines
h o w f ast an a ctio n p oten ti al c an mov e alo n g an axo n : t he rat e o f pa ssiv e s p rea d o f
po t en tia ls is inv e rsely p ro por tiona l to bo t h ax opla s mi c resis ta nc e a n d
m e m bra n e c a pa cita nc e.
Fast con du cti o n of sig n als (b y action po ten tial
p ro p ag atio n ) is c ruci al to the p ro p er fu n ction o f neu r on s so o rg an isms h av e ev o lv ed
two ap p ro a ch es to o v er co min g th e li mitation s in rate o f p assive sp re ad i mpose d b y
elect ro to n ic co nd uctio n . On e so lutio n is to redu c e th e a x o plas mic resistan ce b y
increa sin g th e dia m eter o f th e a xon ( eg. th e gian t axo n of the squid is u p to 1 mm
d iam ete r) to red u ce th e a xo p la s mi c resista n c e. In m a mm als, an ev en mor e c o m mo n
an d ef fe ctive wa y is b y m y elin a tio n o f th e ax o ns.
Ax o n my elina tio n a nd sa lta to ry c on d uctio n
My elin atio n is a way o f r ed u cin g th e m e m b ran e cap acit an c e o f th e ax o n. Th e
cap acitan ce of th e m e mb r an e is criti cally d epen d en t up on m em b ra n e th ic k n ess
b ec au se th e el ectro st atic in t era ction s r esp o nsib le d e clin e with th e squ a re o f th e
d istan ce sep ar atin g th e ch arg es (ions ). The th ick n ess o f th e ax o n al me mb ran e is
g re atly in c re ased b y m y eli na tio n. Du ring d ev elop m ent , n erv e ac cesso ry cells
(call ed Sc h wa n n cells in th e P N S) w r ap th eir pl as ma m e mbr an e lik e a th in tigh t
b an d ag e in a sp ir al f ash io n arou n d e ac h axo n fo r st ret ch es o f ab ou t 20 0
mic ro metr es. Th is my elin sh eat h in c re ase s the distance s ep a rating ions on th e
insid e an d o u tsid e o f th e ax o n , thu s red ucin g th e me mb ran e ca pa citan c e ch arg e.
Bet w een ea ch m y elinat ed seg m en t is a very sh o rt p iec e of b a re axo n m e mbr an e (a
fra ctio n of a mic ro mete r lo n g ) , th e no d e o f R anvie r. Th e a ction potential g en er ated
b y th e o p en ing o f vo ltag e s en sitive so diu m chan n els at th e n o d e o f Ranvi er can
then b e p ro p a g a ted (sp r ea d ) b y th e muc h mo re rap id el ect ro ton ic co n du ction th at is
p o ssib le th ro u g h th e adj ac en t my elin ated se gment (th e intern od e ) to th e n ex t no d e
o f Ran v i er . Th e elect ro to n ic po tenti al sp re ads v ery r apid ly (b ut with di min ish in g
a mp litud e) th ro u g h th e my elin ated s eg ment fro m on e nod e of R an v ie r to th e nex t ,
wh er e th e sig n al is a mp lified (b y vo lt age -de pend en t o pening o f sodiu m ch ann els) .
Th e d ep olaris atio n is th en p ass ed p assiv el y again to th e n ex t no d e . Sinc e th e
actio n p o t en tial mo v es r ap id ly in ju mps th ro u g h th e my elin ated seg men ts bet w een
the n od es of R an vie r, it is k n o wn as sal ta t o ry (ju mping ) co n du ctio n . Salt atory
co n d u ction h as th e ad v an tag es th at it allo w s the actio n p o ten ti al to t rav el mu ch
mo r e q u ickly th an wo u ld b e p ossib le wi th a co ntin uo u sly p r o p ag ated actio n
p o ten tial. Only a s mall f ra ctio n of the ax on (th e no d e seg m en ts) p a rticip ate in
activ e g en e ration o f an a ctio n p oten tial (o p en in g of sod iu m ch an n els) , so v ery
mu ch l ess en erg y is requ i red to m ain tain the con c entr atio n gra dients of th e so diu m
an d po t assiu m ion s (b y th e A T P -po w er ed N a + /K + -pu mp s ) in my elin ated ax o n s.
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Cellular Physiology supplementary notes- Dr Bill Phillips
M yelin a tio n c h an ges the pa ssi ve el ectric a l pro p erties o f th e axo n m e mb ra n e, thu s
increa sin g th e sp r ead o f th e dep olarisin g in ward curr ent, and red u cin g d ela ys.
S ma ll p o rtio n s of th e axo n m e m b rane ( No d e s o f R a n vi er gen era te th e d ep o la risin g
inwa rd cu rrent ( Ho d g kin Cy cle ). W heth er g e n erated a rtifi cia lly b y a sti mu la to r a s
sh o wn , o r na tu ra ll y b y th e H o dg kin C ycle , t h e incr eased me m b rane resistan ce d u e
to th e th i ck , in su la tin g m yelin sh ea th mea ns tha t th e brief d ep ola risin g in ward
cu rrent ca n sp rea d mu ch fu rth er alo ng th e a xon . Th e re d u c ed t en d en cy to stor e
ch a rg e ( ca pa cita n ce ) with in the my elinated in tern o de regio n m ea ns th at the b rief
d ep o la risa tio n mo ves mo r e q ui ckly fro m o n e No de o f Ra n vi er to the n ext . Co mp ar e
this with th e pre vio u s fig u re fo r a non - my elin a ted a xo n .
Th e n eu ro m usc ula r sy na pse
Su mm ary
Th e sy n a p se b et we en so mati c m oto r n eu ro n s an d sk el etal mu s cle fib res is an
ex cita to ry che mi ca l s yn a p se ,
the trans m itter is ac ety lcho lin e ( A Ch ).
Th e
p o stsy naptic me mb r an e con tains a re cepto r fo r A Ch , th e nico tini c A C h re ce pto r
( A C h R) .
Th e n ico tinic A Ch r ec ep tor is a lig an d-ga ted io n ch ann el , a
tran s me mb ran e io n ch an n el th at is o pen ed wh en A Ch b inds to the ex t ra cellu la r
p o rtio n o f th e ion ch an n el p ro tein c ompl ex .
Th e mo to r u nit
E ach limb mu s cle is inn e rv at ed b y a colle ctio n of moto r neu ron s th at a re clu st er ed
tog eth er in the v en tr al h o rn of the spin al co rd (th e moto r n eu ro n poo l of th e
mu scl e) . Th e mo to r n eu ro n p oo l m ay ran g e fr om s ev eral to s ev er al h u n dr ed in
n u mb er d ep end in g o n th e siz e o f the mu scl e an d th e co mp l exity of mo v em en ts it
en g ag es in . Th e ax o n o f e ac h in d ivid u al mo to r neu ron b r an ch es with in th e mu s cle
to fo r m a n u mbe r o f sy n ap s es, ea ch with a d iffe re nt mu s cle fib r e. Th e mu s cle
fib res in n erv ated by a sin g le moto r n eu ron to g ether w ith the mo to r n e u ron itsel f ar e
k n o w n collectiv ely as a m o to r uni t sin ce al l th e fib r es are a ctivat ed and contr act
simu ltan eo u sly wh en an a ctio n p oten ti al co m es d o wn the axo n of th e mo to r n eu ro n .
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Supplementary Notes on Cellular Neurophysiology- Dr Bill Phillips
Th e n u mb e r o f m uscle fib r es within a mo to r u n it c an v a ry b et we en s ev e ral d o zen
an d s eve ral h un d red , d ep en d in g o n th e typ e o f muscl e fib r e.
Th e e nd pla t e po t en tial
Wh en th e mo to r n eu ro n is d ep o la rised to thr eshold an a ctio n p o tenti al mo v es do wn
the ax o n b y saltatory co n d u ctio n . Wh en it reaches the no n -m y elinat ed n e rve
ter min al th e actio n po t en tial spr eads th rou g h all th e bran ch es on the n e rv e t er minal
wh er e it t rig g e rs th e r ele ase o f A Ch. T he A Ch rap id ly d iff uses a cross th e s yn ap tic
cleft an d b in ds to A Ch re ce p to rs , open ing th e ion ch ann el. T he o p ening of th e A Ch g ated ch an nel r esults in so d iu m ente ring the mu scle fib re (in w a rd so d iu m cu rr en t)
an d a me mb ran e d ep o l aris atio n c alled th e E nd Pl ate P ot en tia l ( E P P) .
In
ma m mali an mu scl es th e E PP is u su ally supr a th resh old m ea ning th at ev ery ti m e it
o ccu rs it trig gers a p o stsy n ap ti c a ctio n po ten tial th at rap idly d ep o la rises th e mu s cle
fib re le ad in g to con tr actio n .
Much o f wh at is k n o wn ab o u t th e rel eas e of
tran s mitter d u rin g sy n ap ti c trans missio n h as b ee n infe rr ed by stu d y in g th e
p o stsy naptic me mbr an e p o t en tial ch an g es p ro d u ced b y tra nsmitt er r eleas e .
Th e en d p late p o tential is a v e ry la rge d ep o l a risatio n ( ab o ut Δ70 m V; co mpa red w ith
~1 m V fo r sy n ap tic p ot en tials at c entr al sy n a pses) an d co nsisten tly r aises the V m o f
the m u scle fib r e fro m its restin g v alue o f -90 m V to w ell abo v e th resho ld fo r a
mu scl e actio n p ot en tial.
Rel eas e of tran s mitte r fro m the pr esy nap ti c n erv e te rmin al is v ery rap id an d the
b u rst o f h igh con cent ratio n o f A Ch r apid ly d iffu ses a cross th e syn a p tic cl eft an d
b in d s to th e A Ch Rs o n th e p ostsyna p tic me mb ran e, o p en in g io n ch an n els .
Ho w ev er , mu ch o f th e A Ch in on e bu rst (o r q u antu m) o f tr an smitt er n ev e r r ea ch es
the A Ch Rs o n th e p ostsy n ap tic m em b ra ne . A fter activ ating the A Ch Rs i m medi ately
b en e ath th e site o f r ele ase , th e A Ch , which bin ds reve rsibly to th e AC hR , dif fu ses
a way an d is r apid ly d eg r ad ed by th e enzy m e ac ety l ch o lin este ra s e ( A Ch E ) . A Ch E
h y d ro lyses A Ch to ac etate an d ch olin e . AC hE thu s ensur es that the A Ch re cep to r
ch an n els o p en o n ly bri efly . To stu dy th e me mb r ane cur rents th at ar e respo n sib le fo r
g en e ratin g th e p ostsy n ap tic p o tential , it is nec essa ry to h o ld th e m emb ran e
p o ten tial at a con st an t v alu e as th e A ChRs a re activ ated . Th e ele ctron i c ap p ar atus
that mad e th is p o ssibl e is k n o wn as th e vo l ta ge cla m p.
Vo lt ag e cla mp stu d ies sh o w ed th at th e A C h rec ep tor ch a n nels a re pe r mea bl e to
bo t h Na + a nd K + (bu t n o t anion s) an d that wh en the A Ch R o p ens sod iu m flo ws in
an d p o tassiu m flo ws o u t o f the cell .
E ven tho u gh the K + o utflo w p artially
+
+
co u n te ra cts the Na in flo w , m or e Na flo w s in than K + flo ws ou t ( con sid e r th e
d riv in g fo r ces o n ea ch o f the ion s ),
r e su ltin g in the (net inwa rd ) en d pl ate
p o ten tial.
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Cellular Physiology supplementary notes- Dr Bill Phillips
A t th e n eu ro m usc ula r ju nc tion
Liga n d -g a t ed c ha nn els
A Ch bin d s
Vo l tag e -ga t e d cha n nels
N a + ch an n els op enin g
Ch an n els o p en
N a + flo w s in
K + flo ws o u t
N a + in flo w
D ep ola risatio n
R esul t: e n dpla te p o te n tial
D epo la risation
R esul t: a c tion po t en tia l i n m us cle
fibr es
Tra ns mi tt er r eleas e fro m th e n erv e te r mi n al
With in ab o u t 1 ms o f th e n erv e a ction potent ial re achin g th e ax o n t er min al A Ch is
rele ased , acts o n A Ch R in the postsynapti c me mb ran e an d in itiates th e mu s cle
actio n p o ten tial . The sig n al fo r th e rele ase of t ran s mitte r is th e action p oten ti al
d ep o la risatio n in th e a x o n te r minal b ut n ei th er th e in ward Na + cu rren t no r th e
o u twa rd K + cu rr en t o f th e A P are sufficie n t to trig g er ACh releas e . Instead ,
tra ns mit te r rel ea se is de te r min e d by C a 2 + infl ux i nto t he n erv e te r mi nal. Ca 2 +
lik e N a + is p res en t in mu ch h ig h er conc en tration in the extr ac ellula r fluid th an
insid e th e c ell. Th e ar riv al o f the A P r es ults in the o pen ing o f th e p resy n aptic
v o lta g e -se nsitiv e Ca 2 + c ha n nels , le ad in g t o a ve ry lo calised Ca 2 + in flux . Th e
b rief hig h intr ac ellu lar p u ls e o f C a 2 + is thou gh t to activate to C a 2 + -bind in g
p ro tein s , l ead in g to th e r eleas e o f A Ch .
Qu a n ta l rel ease o f t ra ns mit te r
In tra cellul ar el ect ric al re co rd in g s fro m th e p o stsy n ap tic me mb ran e r ev e aled th at
ev en in th e ab sen ce o f n er v e stim u latio n small d ep o la risatio n s o f a co nsisten t
amp litud e call ed min ia tu re e n dp la te p o ten tials ( me p ps) so meti mes o c cu r .
D ep o la risatio n o f th e n e rv e in c re ases th e fr eq u en cy o f th es e mep p s bu t d o es no t
ch an g e th eir a mp litu d e . Wh en an a ction p oten tial r ea ch es th e n erv e te rmin al it
n o rm ally r esults in an E P P that is comp os ed of th e su m o f ab ou t 15 0 o f th es e
mep p s (the mep p is mu ch b igg e r than the d ep o larisation p ro d u c ed by th e o p en in g o f
a sin g le A Ch R ch an nel: co o rd in ated op ening o f sever al th ousand A Ch Rs co n trib u t e
to a m ep p ) .
Th e v esicl e hypo t hesis h olds th at ea ch m ep p is th e r esu lt o f
ex o cy to sis fr om a rel ease site on th e n erv e te r min al o f th e A Ch co nten t o f o n e
5 0 n m- d ia met er sy n aptic vesicl e co ntaining a standa rd co nc entration o f A C h. The
calciu m co n cen t ratio n d o es n o t ch a ng e th e si ze o f th e q u an tu m o f A Ch rel eas ed (as
me asu r ed b y th e mep p a mp litud e) in st ead t he b rief , lo calised ca l ciu m p u lse is
tho u g h t to in crea s e th e p ro b a b ility th a t a ve sicle o f tra n s mitter will b e rel ea sed at
the r ele ase site . Sin c e th e re a re abou t 15 0 r eleas e sit es p er t er min al this in cre ases
the to tal n umb er of q uan t a rele ase d d urin g ea ch p r esy n aptic action p oten ti al. T h e
total n u mb e r o f q u an t a rele ase d follo win g a sin gle p resyn ap tic actio n p o tenti al is
k n o w n as th e q u a n ta l co n ten t o f th e sy n apse .
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Supplementary Notes on Cellular Neurophysiology- Dr Bill Phillips
A ce ty lc ho lin e r ecy cling
As m en tio ned ab o v e, ac ety lcho lin este ras e ( AC h E) lo cat ed in th e p o stsy n apti c
info ld in g s rapidly hy d ro ly ses A Ch to ch ol in e an d a cet ate . Th e n eu ro n c an no t
sy n thesise ch o lin e an d h en ce must re cycl e cho lin e fro m th e sy n ap tic cle ft. T h e
p resy n ap tic m e mb r an e co n t ain s tr ansp ort er p ro tein s th at h av e a hig h a ffinity fo r
ch o lin e (b u t n o t A Ch ) th at bin d to an d in ter nalise cho lin e in to th e n erv e te r minal .
In sid e th e n e rv e te r min al an en zy me fou n d specifi cally in ch o line rgic neu ro ns ,
ch o lin e a c etyl tra nsfera s e tran sf ers a n ac etat e group to th e ch o lin e and th e A Ch is
rep ack ag ed in to v esicl es v ia th e wor k o f an a ctiv e transp o rt p u m p .
P re - a n d po st -sy na p tic blo c k
Ce rtain d ru g s and to x in s b ind to an d sp eci fi cally b loc k ion ch an n els o n eithe r the
p re- o r p o st -sy n ap ti c m e mb r an es . For exa m p le, toxin s fro m th e v en o m o f marin e
co n e sh ell cr e atu res b in d to voltag e-s en sitiv e cal ciu m ch an n els and blo ck
tran s mitter r ele ase by p r ev en ting C a 2 + f rom flo wing in to th e ner v e t er minal wh en
the actio n p o t en tial dep o laris es th e me mb ran e. On the o th er ha n d , α -bu ng a roto x in
(fro m sn ak es) an d cu r ar e (a plant p rod u ct ) b ind to th e ACh R an d p r even t th e
en d p lat e p o ten tial b y prev en ting the o pen ing o f th o se ch an n els in resp on s e to A Ch
rele ase . Su c h n atu ral b lo ck e rs h ave h elp e d u s to lea rn mu ch o f w h at w e k no w
ab o u t sy n ap tic fu n ctio n .
S Y N A P TI C T R A N S M IS SI O N BE T W EE N N E U R O N S
Un lik e the m u scle fib re , mo st C N S neu ro n s re ceiv e sy n ap tic in pu ts m an y o th er
n eu ro n s , integ ratin g th em in to a d e cisio n wh eth e r to fir e a ctio n p o te n tials.
In d iv id u al neu ron s m ay:
1.
Re ceiv e sy naptic in pu ts f ro m m an y o th e r n e uro n s fro m d if fe ren t p a rts of th e
b rain . Th is is k no wn as co nv erg en ce .
2.
E ach sy n ap tic inp ut ty pi cally c au ses o n ly a s mall sy n apti c p o ten tial ( <1 m V ) .
3.
Man y o f th e s y n ap s es on ea ch n eu ro n ar e in hi b itory rath e r th an ex citato ry .
4.
H av e d if fe ren t ty pes o f tr an s mitter r ec epto rs lo calized at d if fe ren t sy nap s es
o n th eir p las m a me mbr an e. Th ese in clud e bo th dir ec tly lig an d-ga te d io n
cha n nel ty p e r ec ep to rs (eg n icotin ic A Ch R) an d seco n d mess e nge r- cou ple d
re ce pto rs th at m ay c ause slo w er , m or e sub tle ch ang es in th e po stsyn ap ti c
cell.
Ex ci ta to ry pos tsy na pti c po te ntia ls
Glu ta ma te is b eli eved to b e th e m ajor ex ci tatory tr an smitt er fo r c entral n eu ron s .
Mo st g lu ta mat e r ec ep to rs a re ex cit ato ry , m e an ing th ey c au se in w ard (dep o l arisin g
cu rr en ts) called Ex citato ry Po stsy n ap tic Curr ents ( E P SCs ). Th e tran si en t
d ep o la risatio n cau s ed b y th ese E P SCs is calle d th e Ex citato ry Po stsy n apti c
Po ten ti al ( E P S P) an d is ak in to th e E P P in th e mu s cle fib r e .
Th er e a re s ev e ral d i ffe ren t ty p es of g luta ma te re cepto rs th at ar e lig and -gat ed io n
ch an n els; th es e a re d e fin ed ac co rdin g to th e d ru g s th at sp eci fically blo ck th e m.
Th ese in clud e A M P A ty p es, N M D A types as w ell as a s eco nd mess eng e r-link ed
g lu tam ate r ec ep to r ( Q u isq u al ate- B ty p e) .
- The A M P A t yp e g lu ta m a te r ec ep tor ch an n e ls a re resp o n sib l e fo r th e ra p id ea rl y
p h a se of th e ex citato ry po stsy nap ti c p ot en tial ( E PS P ) .
- N M D A t yp e r ec ep to rs req u ire b oth gluta m ate b ind in g an d d epo larisatio n of th e
m e mb ra n e b efo re th ey op en a n d ar e resp o n sible fo r a lat e contribu tion to th e
E PS P .
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Cellular Physiology supplementary notes- Dr Bill Phillips
Inhi bito ry pos tsy na p tic po te ntia ls
Th e major i n hibi to ry tra ns mit te r in the b rain is G A B A (g a m ma- a min ob uty ri c
acid ) . Ano th e r i mp o rtan t in h ib ito ry t ran s mi tter fo r th e so m atic mo tor n eu ro ns is
g ly cin e .
In h ib ito ry neu rotr an smitt ers wor k main ly b y ope nin g Cl - c ha nn els
(so m etim es K + ch ann els)
N ern st p oten ti als fo r Cl - ( an d K + ) a re neg ativ e [ E C l ≈ -70 m V, E K ≈ -75 m V ].
Op en in g o f a ligan d -g at ed Cl - ch ann el c an in hib it d epol arisation b y:
1.
2.
3.
Hy p erp o larisin g a n eu ro n to w ard s the E C l .
Th e Cl - co n d u ctan ce c an "cla mp " V m at E C l , p rev en ting in w ard curr en ts fr o m
raisin g V m .
Th e Cl - co n d u ctan ce c an a ct as a s h u nt o r sho rt ci rcuit , dissip ating th e lo cal
circu it cu rr en ts ac ro ss the me mb ran e bef o re th ey rea ch th e trigg er zo n e at
th e ax o n h illo ck wh e re a ctio n po tentials a re i n itiated .
G A B A r ec ep to rs h av e b in ding sites fo r b enzo d i az epin es (e g. V aliu m) an d
b arb itu r ates: b ind in g of eith er o f these d rug s to their bin ding sites on the G A B A
rec ep to r in cr eas es the af fin ity o f G A B A fo r its b in din g site, th us in c re asin g th e
eff ectiv en ess o f in h ib ito r y in puts to n eu ro n s.
N eu ro na l i nt eg ra tio n
A sing le moto r ne uron c an h av e u p to 1 0,0 0 0 p resy n aptic in p u ts
N eu ro n al integ ratio n is the d e cision o f th e neu ro n to fire o r n o t to fi re an
actio n p o ten ti al
Th e a x o n hillo c k h as a high con c entr atio n o f Na + c hann els an d lo w er
th resh o ld (th e trig g er zo n e); a ction p ot ential s (sp ik es) origin ate th e re .
Te m po ra l a n d s pa tial s u m ma tio n
Bo th E P SPs an d I P SPs d e clin e in a mp litu d e with tim e and with d istan ce alon g th e
d en d rites fro m th e so u r ce (th e sy n aps e) , d u e to th e pa ssiv e ele ctrical p rop erties o f
the n eu ro n .
D eclin e with tim e: m easu red by th e me m b r ane ti me cons ta n t . In neu ro ns with a
lon g time co nstan t , EP S Ps a re slo w to d ec a y so seq uen ti al E P SPs can o v erl ap an d
su m tog eth e r
to mak e a l arg er dep o l aris atio n .
This is k no wn as t e m po ra l
su m ma tio n .
D eclin e with distan c e alo n g th e d end rite: m e asu r ed b y th e l eng th c o ns ta n t. I n
n eu ro n s with lar g e len gth co n st an ts E P S Ps fr om distant s yn ap s es can mor e
eff ectiv ely ad d to geth er at th e trig g er zo n e to r ea ch th resho ld . This is kn o wn as
spa tia l su m m a tio n .
69