Lecture 3 - Action Potential Conduction

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    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 aon 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 thatwith melin. Also, the membrane has capaciti*e properties /stora!e of char!e 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 aon depends on the membrane len!th constant,

    /lambda.

    - measures how uic"l a potential difference decas to 3ero as a function of distance.

    - The !reater lambda is, the better is the aon at conductin! a si!nal. The depolari3in! currentwill spread further down the aon and elicit aon potentials of !reater len!th.

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    - There are 2 strate!ies to increase 4 increase the diameter of the aon, this will allow current to

    tra*el easier throu!h the interior of the aon. The other strate! is to increase membrane

    resistance so that we don#t !et *olta!e lea"in!.

    Short

    - $ad conductor- 5ast deca of the potential difference

    on!

    - 7ood conductor- 5aster impulse conductance

    - ose less potential difference as it mo*es alon! the aon

    - The farther a threshold-depolari3in! current spreads alon! an aon, the shorter the time it ta"es

    for the impulse to reach the end of the aon

    en!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 euation. The ratio is membrane

    resistance /8m o*er internal resistance /8i. )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.

    en!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 :;acent nodes and can tra*el man

    nodes down the aon and successfull depolari3e the membrane to the threshold. The A canmo*e ? to 10 nodes down the aon and !enerate As successfull. +ithout the melination,ou could ne*er !et that far.

    - $ut the lar!er the diameter of the aon, 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

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    time is the openin!closin! 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 aons

    - Falf the aons in the ner*ous sstem are not melinated. %nl the ones that ha*e to sendinformation uic"l are melinated.

    - )n unmelinated aons, both &aB and B channels are intermied. This means we will see an

    after-hperpolari3ation.- The unmelinated aons are thin /not lar!e and ha*e slow conduction. The conduction *elocit

    will ob*iousl be *er slow because of the small aon diameter and low membrane resistance.

    - A sin!le !lial cell /Schwann cell will en!ulf a whole bundle of aons 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 aons /about

    :0 aons.

    Aon Terminal- %nce the A has started, it will tra*el throu!hout the membrane and each A will !enerate a

    new one net door and !et this chain reaction all the wa to the end. +hat happens at the end of

    the aonD The A cannot !o bac" where it came from because of the refractor period.- +e find an enlar!ement at the aon terminal, called a bouton, because the loo" li"e buttons.

    Aons 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 thecalcium /Ca2B 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 seuestered outside the membrane. 8emember that the !lcocal /which

    has a ne!ati*e char!e seuesters 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 eoctosis of these *esicles located in the bouton. The

    *esicles will fuse with the bouton membrane and release their contents into the etracellular

    fluid.

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    - 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"eslittle time, about 0.2 milliseconds, and then binds to receptors on the membrane of the other

    neuron.

    Snaptic *esicle /top-ri!ht

    - 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 eoctosis process. The proteins enable the

    process of fusion with the cell membrane.

    9esicle 'oc"in!

    - The *esicles are assembled for release around apolhedral scaffold4 we ha*e a Greadil releasable pool#

    of *esicles.

    - The eoctosis process will occur as soon as the calciumions are recei*ed.

    9esicle 8elease

    - There are 2 tpes of eoctosis4 "iss-and-run eoctosis /*esicle fuses for 100 ms and part of

    its contents will be released, so it ta"es man fusions before it completel empties its contents.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 eoctosis is G"iss-and-run# tpe.

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    - 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 bereleased. )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 eoctosis process.

    - S&A8E proteins are found both at the fusion pore /the site where *esicle will fuse with themembrane of bouton and in the *esicle membrane. The >oinin! to!ether of S&A8E proteins

    /in *esicle and bouton membrane 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 aonal bouton and the membrane of an ad>acent neuron.

    - The snaptic cleft is about 200 an!stroms wide /standard distance.

    - &eurotransmitter a!ent diffuses across the snapse and binds to a specific site on a receptorprotein 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.

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    - )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!and.

    - =etabotropic4 the receptor protein has en3me properties which are acti*ated upon bindin! oftransmitter. +e will discuss details of this in net lecture.

    Electrotonic snapse- A different classes of snapses that do not function chemicall /no transmitter is released from

    *esicles. 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!stromsapart and the !ap is brid!ed b tubular proteins /conneins which tra*el from the interior of

    one cell ri!ht into the interior of another cell. The conneins 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 actto!ether as a functional unit. 5or eample, 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 areinhibitor 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.

    &et lecture4 what happens at ionotropic and metabotropic receptorsD