Lecture 3: Action Potential Conduction

September 16, 2011

Electrical Conduction
- Action potentials use electrical current because it is superfast. The low current densities do not
cause an tissue dama!e.
- A membrane is not too thic" so it doesn#t ta"e much time for an ion to diffuse throu!h that. $ut
toda we are tal"in! about C%&'(CT)%& o*er centimetres. +e can#t use diffusion with that,
we ha*e to use electrical currents. )f we were to use diffusion, the free ions would not diffuse
*er far before bein! bound or transported out.
Cable -roperties
- Thin" of the interior of an a.on as a bi! wire.
- +ith copper wires that are insulated, we will still recei*e the same *olta!e at the end of the
wire that we recei*ed at the startin! point. +ith membranes, the *olta!e 10 centimetres awa
would be much less in comparison to what we started with. Also, the si!nal would be distorted.
This is because we ha*e lea"a!e of current snea"in! across the membrane, we can reduce that
with melin. Also, the membrane has capaciti*e properties /stora!e of char!e0, this can lead to
distortion of shape.
+e want to impro*e the cable properties as much as possible.

- The conduction
*elocit of an action potential alon! an a.on depends on the membrane len!th constant, 1
/lambda0.
- 1 measures how 2uic"l a potential difference decas to 3ero as a function of distance.
- The !reater lambda is, the better is the a.on at conductin! a si!nal. The depolari3in! current
will spread further down the a.on and elicit a.on potentials of !reater len!th.
- There are 2 strate!ies to increase 14 increase the diameter of the a.on, this will allow current to
tra*el easier throu!h the interior of the a.on. The other strate! is to increase membrane
resistance so that we don#t !et *olta!e lea"in!.
Short 1
- $ad conductor
- 5ast deca of the potential difference
6on! 1
- 7ood conductor
- 5aster impulse conductance
- 6ose less potential difference as it mo*es alon! the a.on
- The farther a threshold-depolari3in! current spreads alon! an a.on, the shorter the time it ta"es
for the impulse to reach the end of the a.on
6en!th Constant
- This is a measure of passi*e spread of electrical current, as in an conductor. The spread of a
depolari3in! current is the mechanism of action potential conduction.
- Stuff in the denominator dominates, so we can simplif our e2uation. The ratio is membrane
resistance /8m0 o*er internal resistance /8i0. )f we increase the membrane resistance, we !et a
lar!er lambda, and if we decrease the internal resistance we !et a lar!er lambda.
6en!th Constant
- )f we impose a potential difference across a membrane at a particular point, and if the A- is
about 100 m9 in amplitude, the measured *olta!e will decrease in space and where it hits :;<
of the ori!inal *alue, that#s defined as the lambda /the len!th constant for that membrane0.
6ambda for cell A is shorter than cell $. Cell $ is !oin! to conduct a si!nal much further than
cell A. 6ambda is much better in cell $. Cell $ will ha*e a faster conduction *elocit, the
depolari3in! currents will tra*el much further down the membrane and !enerate A-s much
further.
=elination
- To increase the resistance of a membrane, we use melination.
- Speciali3ed !lial cells /Schwann cells or oli!odendroctes0 help neurons b creatin! an
increased membrane resistance4 there is less lea"a!e of current out into the e.tracellular space.
- The !lial cells wrap around the a.on man times. +e are literall pilin! up more and more
membrane. This creates a melin sheath, which !reatl increases resistance of the membrane.
- Ad>acent !lial cells will usuall ha*e a !ap between them, and it#s referred to as the node of
Ranvier.
- +ithin the C&S, oli!odendroctes do the e.act same >ob as Schwann cells do in -&S. $ut
Schwann cells wrap around >ust one section of one a.on, all the ctoplasm is e.truded. The
oli!odendroctes do the same thin!, but wrap around man a.ons, the are li"e an octopus with
arms wrappin! around different a.ons.
- The node is the onl place where the a.on membrane is e.posed. This is where membrane
resistance is relati*el low, so lea"a!e does occur.
Saltator Conduction
- )n melinated a.ons, onl the membrane that is e.posed at the nodes is e.citable.
- Action potential >umps from one node to the ne.t ? to 10 nodes. -assi*e spread of depolari3in!
current occurs between nodes.
- At the nodes, we !et an influ. of sodium ions from the e.tracellular space. Saltator means
@>umpin!A, the A- is >umpin! from node to node, it is not created in between the melin sheath.
&ode of 8an*ier
- Contains hi!h densit of *olta!e-!ated &aB channels /1000 to 2000 per s2uare micron0.
- &o *olta!e-!ated CB channels means no after-hperpolari3ation
- )n the dia!ram, blue is the node, and this is where we ha*e hi!h densit of *olta!e-!ated &aB
channels. That#s where the channels are useful, there is no use in steppin! them under the
melin. The all mo*e to where the can be useful4 the node.
- )n the paranode, which is >ust near the endin! of the melin sheath, all the *olta!e-!ated CB
channels are located.
- The node is the !ap. $lac" dots are the *olta!e-!ated &aB channels. 9olta!e-!ated CB channels
are pushed to the side, the are represented b open circles.
- This means that an A- !enerated in the node is not !oin! to ha*e a si!nificant hper-
polari3ation because there is *er little contribution of the *olta!e-!ated &aB channels.
- )mportance of a.on diameter4 the inter-nodal spacin! is proportional to the diameter of the
a.on. The lar!er the diameter of the a.on the lon!er the distance in between the nodes.
- The depolari3in! currents !enerated at the A- tra*el down ad>acent nodes and can tra*el man
nodes down the a.on and successfull depolari3e the membrane to the threshold. The A- can
mo*e ? to 10 nodes down the a.on and !enerate A-s successfull. +ithout the melination,
ou could ne*er !et that far.
- $ut the lar!er the diameter of the a.on, the less the internal resistance. The depolari3in!
currents will tra*el much faster. )n $, there is a lar!er lambda.
There is also faster conduction *elocit.
- These electrical currents are tra*ellin! alon! instantaneousl. +h does it ta"e milliseconds for
si!nals to tra*el 10 cm awaD )t ta"es a measurable amount of time to do that. +hat ta"es the
time is the openin!Eclosin! of &aB channels. These currents don#t mo*e the whole distance,
the onl !o ? to 10 nodes at a time, and then depolari3e the membrane, openin! of the
channels occurs etc.
(nmelinated a.ons
- Falf the a.ons in the ner*ous sstem are not melinated. %nl the ones that ha*e to send
information 2uic"l are melinated.
- )n unmelinated a.ons, both &aB and CB channels are intermi.ed. This means we will see an
after-hperpolari3ation.
- The unmelinated a.ons are thin /not lar!e0 and ha*e slow conduction. The conduction *elocit
will ob*iousl be *er slow because of the small a.on diameter and low membrane resistance.
- A sin!le !lial cell /Schwann cell0 will en!ulf a whole bundle of a.ons without windin! around
indi*idual ones. )t#s still better than no insulation. These bundles are "nown as GRemak
bundles#.
'ia!ram of 8ema" bundle4
- The !lial cell has en!ulfed a set of a.ons /about
:0 a.ons0.
A.on Terminal
- %nce the A- has started, it will tra*el throu!hout the membrane and each A- will !enerate a
new one ne.t door and !et this chain reaction all the wa to the end. +hat happens at the end of
the a.onD The A- cannot !o bac" where it came from because of the refractor period.
- +e find an enlar!ement at the a.on terminal, called a bouton, because the loo" li"e buttons.
A.ons end in boutons which are filled with *esicles. The *esicles are filled with chemical
a!ents that act as neurotransmitters. Fow do we release those *esiclesD
- The membrane of the boutons contains another *olta!e-!ated channel, which is specific for the
calcium /Ca
2B
0 ion. This channel is opened b depolari3in! the membrane of the bouton, and
this depolari3ation occurs than"s to the action potential currents. The threshold is around -?0
m9.
Calcium is usuall se2uestered outside the membrane. 8emember that the !lcocal. /which
has a ne!ati*e char!e0 se2uesters calcium ions outside the membrane. +hen calcium channels
open due to depolari3in! currents from the A-, calcium diffuses into the cell.
- &ow calcium tri!!ers the process of e.octosis of these *esicles located in the bouton. The
*esicles will fuse with the bouton membrane and release their contents into the e.tracellular
fluid.
- The presnaptic membrane of the bouton is ali!ned with the membrane of another neuron, and
there is a cleft in between the two, and this is called a synapse.
- The neurotransmitter that is released simpl has to diffuse across 200 an!stroms, which ta"es
little time, about 0.2 milliseconds, and then binds to receptors on the membrane of the other
neuron.
Snaptic *esicle /top-ri!ht0
- The loo" prett scar from the outside. There are all "inds of proteins stic"in! out from their
membrane, these proteins are important for the e.octosis process. The proteins enable the
process of fusion with the cell membrane.
9esicle 'oc"in!
- The *esicles are assembled for release around a
polhedral scaffold4 we ha*e a Greadil releasable pool#
of *esicles.
- The e.octosis process will occur as soon as the calcium
ions are recei*ed.
9esicle 8elease
- There are 2 tpes of e.octosis4 "iss-and-run e.octosis /*esicle fuses for 100 ms and part of
its contents will be released, so it ta"es man fusions before it completel empties its contents0.
5or hi!her rates of si!nallin!, we want full fusion4 the whole *esicle contents are dumped into
the cleft in one swoop.
- $ut usuall, *esicle e.octosis is G"iss-and-run# tpe.
- The whole process of releasin! *esicles is probabilistic. +hen the A- arri*es at the boutons, it
is possible that a *esicle will be released, but there is onl a probabilit that a *esicle mi!ht be
released, and there is a H0< probabilit that 2 *esicles will be released, and 10< that : will be
released. )t#s impossible to predict this. 1 action potential has a 10 to I0< chance of releasin! 1
*esicle.
S&A8E -roteins
- There is complicated machiner in*ol*ed with the e.octosis process.
- S&A8E proteins are found both at the fusion pore /the site where *esicle will fuse with the
membrane of bouton0 and in the *esicle membrane. The >oinin! to!ether of S&A8E proteins
/in *esicle and bouton membrane0 is accomplished b calcium, the influ. of calcium binds
these S&A8E proteins and initiates the fusion of *esicle membrane with the bouton membrane.
The contents of the *esicle then diffuse into the snaptic cleft.
- The calcium channels are phsicall situated ri!ht beside the fusion pores. The calcium comes
ri!ht where the S&A8E proteins are, so that it can bind immediatel and initiate the whole
process.
Snapse
- The snapse is a !ap between a.onal bouton and the membrane of an ad>acent neuron.
- The snaptic cleft is about 200 an!stroms wide /standard distance0.
- &eurotransmitter a!ent diffuses across the snapse and binds to a specific site on a receptor
protein embedded in postsnaptic membrane.
The bindin! of transmitter causes a conformational chan!e in the shape of that receptor protein.
- The receptor can be one of two classes4 ionotropic or metabotropic.
- )onotropic4 the receptor will open an ion channel when the transmitter is bound. This is a
li!and-!ated ion channel /the transmitter is the li!and0.
- =etabotropic4 the receptor protein has en3me properties which are acti*ated upon bindin! of
transmitter. +e will discuss details of this in ne.t lecture.
Electrotonic snapse
- A different classes of snapses that do not function chemicall /no transmitter is released from
*esicles0. The ad>acent cells are phsicall connected to one another throu!h tubular proteins.
This is "nown as a !ap >unction4 ad>acent membranes are *er close to!ether, :? an!stroms
apart, and the !ap is brid!ed b tubular proteins /conne.ins0 which tra*el from the interior of
one cell ri!ht into the interior of another cell. The conne.ins allow small ions and depolari3in!
current to cross the !ap. So the depolari3in! current will depolari3e the membrane of the
ad>acent cell, open up &aB channel and create an A-.
- $ecause of electrotonic snapses, all cells will produce the same si!nal. An A- in one will be
transmitted automaticall in all other cells. )n chemical snapses, we don#t e*en "now if the
*esicle is !oin! to be released.
- These electrotonic snapses are found in !roups of neurons or muscle cells that we want to act
to!ether as a functional unit. 5or e.ample, in the heart muscle, smooth muscle, uterus, and parts
of the !ut. $ut the are also found in !roups of neurons. )n the cerebral corte., there are
inhibitor neurons that are lin"ed to!ether b electrotonic snapses. These inhibitor neurons
are in the same phase of acti*it, the all act to!ether.

&e.t lecture4 what happens at ionotropic and metabotropic receptorsD