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					Part III- the action potential
                ‫הודעות‬


           from neuron to :‫• ספרים מומלצים: להולכה פסיבית‬
                               )4-5 ‫(פרקים‬brain/Nicholls
‫ (פרק‬principal of neural science/Kandel :‫• לפוטנציאל פעולה‬
                                    nicholls‫9) או פרק 6 ב‬
                  Rehearsal

As we said
• Membrane potential is the adjusted sum of equilibrium potential
  of it’s ions )mostly K, also Na and Cl(.
  These are all concentration dependent channels.
  Which other type of channels are possible?
• The flow for each Ion is determined by it’s conductance and
  driving force. The flow in each channel can be described by
  V=IR.
  In which cases is the curve non linear?
• The entire flow can be described as parallel RC circuit.
  time constant is τ =RC, (exponential increase)

• The membrane also serve as a cable: Input is transmitted till
  trigger zone where action potential is created and it is
  transmitted from there to axon.
                            rm
Space constant is      l=              and resistance can be
  retrieved.                ra
Axonal size effect R’s )preserves voltage better(-safety factor,
  myelin…
Conductance velocity is determined by l & t.
                  the paradigmatic view


• Input arrive to dendrites in the form on Voltage change.
• Voltage flow passively to axon hillock
• In axon hillock starts the active process of Action Potential.
• Action potential travels (regenerated) along the axon to cause
  Transmitter release in the synapse (gap) between neurons.
  This is the output
• Transmitter attaches to receptors in dendrites of following
  neuron, causing voltage change…

(starting point sensing receptor-skin, eyes… end- muscle. All that
   is in the middle between sensation and action, is in the input-
   output relationship, somehow…(
                   The action potential- phenomenology



Shortly: It’s an electrical signal –
  high amplitude (up to 100mV)
  lasting ~0.5-1ms
  non-attenuated

The ending first: positive
  feedback through depolariztion
  dependent Na channel,
  followeed by a negative
  feedback through
  depolarization dependent K
  channel
                  Action potential phenomenology -
                  different time periods

• A-resting potential
• B-threshold
  (sufficient
  depolarization),
  followed by rapid
  depolarization until
  a certain peak
• C-re-polarization
• D-after hyper-
  polarization
                    The action potential phenomenology-
                    what would you check for?

•   You have intra- and extra-cellular recordings
•   You can change the stimulus
•   You can try dissociating ions (how)
•   You can influence Vm (how?)

=>What would you do to DECRIBE the phenomena?
                     The action potential- phenomenology
                     (what Hodgkin did) I


                                                    all
Threshold- “all or none” either full action
  potential, or nothing
 (note- “big enough stimulus” can indicate bigger
  amplitude of stimulus or longer duration)


(first intuition- what does it tell us about the
    mechanism? can it be dependent solely on
    driving forces changes?)



                                                    None
                                                              The action
                                                                potential
                                                             mechanism-
                   1. it’s the conductance

• If it was the driving force it would be linear (no threshold)
• Also, Curtis found it (Cole and Curtis, 1938) :




How would we call such I-V curve? What it is assumed to be
  influenced by?
(note: this dependence start at about half of the voltage of the
  AP threshold- the process starts before)
                                                             The action
                                                              potential
                                                            mechanism




• How can g be calculated? Ii=gi(Vm-Veq) =>gi= Ii/ (Vm-
  Veq). In voltage clamp we manipulated Vm and measure
  I- we can extract g.
• But not in intra-cellular recordings since g & Vm are
  now interdependent g(Vm)             Vm(g)

                              Vm is controlled(Vm=Vc) in voltage clamp

                                   dV
                                       =0
                                    dt
                                   IC = 0
                                   I total = I R
                  The action potential- phenomenology
                  (what Hodgkin did) II

Refractory period
• Absolute: No amount of current will produce a second action
  potential
• Relative: Second action potential will be achieved with only with
  larger currents (threshold increased)
                  The action potential- phenomenology
                  (what Hodgkin did) III

Accommodation - extension of the refractory period concept-
• If a cell is held (by voltage clamp!) at long sub- threshold
  depolarization, threshold increased (analogous to relative
  refractory period)

Also taken to the extreme-a big/long enough depolarization will
  increase threshold to ∞ (analogous to absolute refractory
  period)- Depolarization block


• Also opposite- if held at hyper- polarization, threshold
  decreases. With enough hyper-polarization- Vm is above
  threshold (anodic break response)
                The action potential mechanism-
                what did Hodgkin & Huxley check?



• Is it all ions or part? Separating ion currents
• Understanding the mechanism causing ion changes
                                                          The action
                                                           potential
                                                         mechanism
                   2. it’s not all ions

• Overshoot- if permeability would have been increase for all
  ion the maximal peak of the action potential would have
  been 0mV. It’s bigger )Hodgkin and Huxley, 1939(




What is it closer to?
(1909-K is in repolarization. 1945-K is sufficient)
So far we know that there are:

depolarization dependent Na channels->positive feedback
Later depolarization dependent K channels->Negative feedback
What can this alone explain?

How can we prove it is Na and K indeed?
                                                                The action
                                                                 potential
                                                               mechanism
               3.Separating ions- several methods

• Changing concentration of extra-cellular ions. Or better-
  exchange (putting choline extra-cellularly instead of Na (why is
  it better to put something instead?) .problem-changes more
  then we wished.
• Changing Vm (by voltage clamp)(note- NO AP!)




• Specific toxins, if you have ones, of course.


                                                  TTX is one
                                                            The action
                                                             potential
                   Separating ions-results from            mechanism
                   concentration change

• The amplitude of the action potential increase as
  extra-cellular concentration of Na are increased.
=>:the amplitude of the action potential is due to Na current!

If Na was replaced by choline
What would have happened?
                                                  The action
                  Separating ions-results from     potential
                  Voltage clamp                  mechanism



• A fuller explanation: When
  voltage is held constant above
  threshold there is inward current
  (which ion would move inward
  passively?), followed by outward
  current (which ion would move
  outward passively?)

• The inward current is Na, K is
  probably outward (no proof yet)
• Notice I-K is slower. Why?
• Notice II- Na stops while stimulus
  continue- why?
                                                      The action
                                                       potential
               Separating ions-results from toxins   mechanism




• TTX - High affinity voltage
  dependent Na+ channel blocker
  (also Saxitoxin and cocaine to a
  lesser extend) ), proves that
  early current is Na- a specific
  voltage dependent channel!

• TEA - Low affinity voltage
  dependent K+ channel blocker
  (also apamin), proves that later
  current is K- a specific voltage
  dependent channel!
How did they find the right ions?




Changing concentrations, voltage clamp,   specific toxins
                                          (with voltage clamp)
                  Rehearsal

• Each ion current’s direction is determine by Nernst, Vm by all
  ions that have channels (dependent on their Z)
• Ion pass passively according to V=IR, with an exponential
  charge (rate dependent on t=RC), and decay (rate dependent
  on l = rm )
            ra

• In parallel, depolarization dependent Na and K channels exist in
  the cell (highest distribution- on the axon hillock, the
  paradigmatic “spike initiation zone”(. H & H found that action
  potential is due to conductance change )“depolarization
  dependent”(, leading to first a flow of Na, then K.
Re-constructing the currents:
• Na faster and Stubbed,
• K slower and longer

Open questions-
• Why is Na faster then K?
• Why is NA current terminated while
  K continues?
How did they find the right ions?




Changing concentrations, voltage clamp,   specific toxins
                                          (with voltage clamp)
                                                            The action
                                                             potential
                   The basic mechanism                     mechanism




• Conductance increase and is voltage dependent
• The ions flowing are first Na (inward) until peak, followed by
  K (outward)

Conclusion about mechanism- positive feedback for Na
   causes rapid depolarization.
Negative feedback for K causes later
re-polarization (maybe also after-hyper
polarization?)
Re-constructing the currents:
• Na faster and Stubbed,
• K slower and longer

Open questions-
• Why is Na faster then K?
• Why is NA current terminated
  while K continues?
                                                         Explaining
                                                    phenomenology

                Explaining phenomenology- threshold

Two possibilities-
1. Enough voltage is needed to open the voltage
   dependent channels?
2. Enough Na current (in voltage dependent channel) is
   need to overcome K hyper polarization to create
   positive feedback
-what do you think?
-How would you test it?
                                                         Explaining
                                                    phenomenology
                 Explaining phenomenology-
                 the action potential
• Resting potential Σcurrent=0 -> K=Na+Cl -> K>Na
With depolarization Na voltage dependent channels open (K not
   yet), increasing Na threshold: Na=K.
Then Na increase to create depolarization to increase… this is
   the rapid depolarization. Maximal peak= ENa (55mV)
Maximal peak isn’t always reached:
K voltage dependent current opens,
Causing hyper-polarization and the
re-polarization and
after-hyperpolarization phases.
                                                         The action
               Evidences from single channel              potential
               recording                                mechanism



• From a much later times, when there were single
  channels recording and Na voltage dependent channel
  was known (and traceable)
                                                     The action
               more issues :                          potential
               1. what do we see in voltage clamp   mechanism




Voltage dependency:
what do we see?

Reversal potential
                                                           Explaining
                                                      phenomenology

                 2. The currents

• currents dependency on voltage- as extracted from
  voltage clamp:
                                                             K
                                     I-V curve




K current is outward above -60mV
inward below
                                   outward              Na
Na current is inward, decreasing
when bigger then 0mV and outward   intward
above 55mV. Why the decrease?
G and driving force interplay
                  3. conductance

• Conductance time dependency as extracted from voltage
  clamp
gion=Iion
     Vm-Eion

=>Well someone will have to
explain this Na inactivation
Someday…
                   Explaining phenomenology- what is
                   missing here?

• We are yet unable to explain refractory period and
  accommodation, so lets do discuss this inactivation..
Activation: Increased probability of channel opening with
  depolarization (in case on voltage sensitivity).
Deactivation: the natural closing of the channel.
Inactivation- active blocking of a channel (a type of control
  mechanism over opening type)
De-inactivation- the natural ceasing of the inactivation
  process…

=>The Na Channel
goes through
inactivation
                                                       Explaining
                                                  phenomenology

                    The PEAK conductance

•   Conductance (peak conductance!) voltage dependency as
    extracted from voltage clamp:

gion=Iion
     Vm-Eion

1. Conductance is
monotonically increasing
2. It isn’t an exponent, it’s a
Sigmoid (several exponents,
Indicating reaction of higher
degree)
                                                   HH model


                  A second look at conductance

We have two channel (for K and for Na) that are:
• Voltage dependent
• Sigmoid (few exponents)
  Shaped
• Similar, but not identical
  (K is more sigmoid then Na)
• Na have inactivation
  (why not visible in the
  voltage dependency graph?)
                Introduction to action potential- first
                order reactions

                                              b
                               open                      close
                                          a
                                 1-n          α(V)   n
                                 closed       β(V)   open
Probability to open a channel is a
Probability to close a channel is b
(P(close) ≠1-P(open) )
Voltage dependent=>a,b changes with voltage
                                                                1
                                                          t=
An exponential process with                                  (a  b )
                                                
                                                       t
                                                            
   = a 1  n   bn
dn
                               n = n (V )1  e   t n (V ) 

dt                                                         
                                                           
At a given V, n will approach n∞ in an exponential rate with time
constant t bigger a,b, faster reaching n ∞(
                                                                For specific V
       At equilibrium
                                                 = a 1  n   b n
                                              dn
     dN                                      dt
         =0                                     1     dn             a
      dt                                                 = n 
                        a                     a  b dt             a b
     N (t =  ) =
                    (a  b )                             dn
                                              t n (V )          = n  n(V ) 
                                                          HH model

                  The Hodgkin Huxley model for
                  channel conductance )“gating model”(

Assumptions:
• membrane can be describe by RC circuit analogy
• Membrane channels are separated and independent of each
  other
• Membrane channel are ion selective
• Membrane channel transit between two states- “open” and
  “close”

                            a nclose
First order reaction nopen               a is the probability to
   open. b to close.        b
   a & b are independent of each other (as if there are infinite
   ions). How many gates will be open at equilibrium?
                                                                  HH model

                      For a first order reaction (Hodgkin
                      Huxley):

If a is P(open), b=P(close)             1-n          α(V)     n
n opened, 1-n closed
                                        closed       β(V)     open
                                                            n ∞ =a/a+b
                    = a 1  n   bn
Then a change is
                 dn
                                                            t=1/a+b
                 dt
exponential increase and decrease
                                                 = a 1  n   b n
                                              dn
                    
                           t
                                             dt
   n = n (V )1  e   t n (V ) 
                                                1     dn             a
                                                       = n 
                                            a  b dt             a b
                                                         dn
                                                 t n (V ) = n  n
                                                         dt
                                                    HH model
               K+ conduction is sigmoid= 4 first order
               reactions=4 n gates


                      n∞
                                  n
   g K (V , t ) = g K n   4
                                      n4
   0  n 1


With a pencil, H& H found
that 4 mounted exponents
fit the K sigmoid
=>The K channel have 4
gates, opens only when all
have opened
                                                      HH model

                 Na+ conduction is sigmoid= 3 first
                 order reactions=3 m gates



     g Na (V , t ) = g Na m   3


     0  n 1
With a pencil, H& H found that 3
mounted exponents fit the K sigmoid
=>The Na channel have 3 gates (m)
and an inactivation gate (h)
  opens only when all have opened
                                                    HH model

                  Implications I- the voltage dependent
                  element is a & b

• For gates N and M-a increase      β       α
  with depolarization, b decrease




                                                V

• For gate h- M-a decrease              α       β
  with depolarization and b increase
                      Gates time constants

Dependence of time constants on voltage: m only in
depolarization, n& h are slower at it (but available
also in hyper -polarization

       m




                                                       Time constants at
                       h                               threshold depolarization:
                                                       M>n~>h
                                        n
               Gates voltage sensitivity

• Dependence of
  channels on
  depolarization>m>h
                                                                            HH model


                  The final Hodgkin Huxley equations


        = I ext  g l Vm  Vl   g K n 4 Vm  VK   g Na m 3 hVm  VNa 
    dV
C
     dt
        dn
t n (V ) = n  n (V )
        dt
        dn
t m (V ) =  m  m (V )
        dt
        dh
t h (V ) = h  h (V )
        dt

 M=α (u) (1 - m) - β (u) m
 N=α (u) (1 - n) - β (u) n
 H=α (u) (1 - h) - β (u) h
                  The Hodkgin-Huxley model of action
                  potentials - currents

               I C =  I R  I ext                        L-leak (passive
                                                               channels)
                dV
               C =  I l  I K  I Na  I ext
                dt


  dV
C    =  gl (Vm  El )  g K n 4 (Vm  EK )  g Na m3h(VNa  EK )  I ext
  dt

  dV
C    =  g l (Vm  El )  g K (Vm  EK )  g Na (Vm  ENa )  I ext
  dt
                           Real numbers

                        25  v
a m v  = 0.1
                 exp 25  v  /10 1
bm v  = 4 expv /18
                         10  v
a n v  = 0.01
                  exp 10  v  /10 1

bn v  = 0.125expv /80

a h v = 0.07expv /20
                        1
 b h v  =
              exp 30  v  /10  1

                                        g Na = 120   g K = 36   g L = 0.3
                                                          HH model

                          Evidences- a biochemical model for
                          the gates and inactivation
                                Basic structure




Armstrong and Benzilla,
1977

The ball and chain            And the K channel as 4
model for                   voltage sensitive domains
inactivation
                 3-D Na+ (and Ca+) channel specificity

• (Na is smaller then K) outer mouth:2 p loops with
  glutamic acid (-), select cations
• inner mouth: 0.3x0.5nm pore )enough for Na+•H20 or
  smaller-not K)
                                        HH model


More elaborated structure (Na and K)


                                 Shaker A type K+
                        pore     channel

                         voltage sensor

                        Inactivation segment

                                 Voltage
                                 activated Na+
                                 channel
         Selectivity filter (both Na and K)



For K:
                Ion flow

Voltage sensor -S4 helix
• Present in all voltage
sensing channels
• Every 3rd residue is a charged lysine or arginine
• Depolarization causes movement of their C termini from
  cytosolic to exoplasmic surface → gate opening
• Activation involves movement of 12-14 charges

Inactivation segment-
• Na+ channel: Cytoplasmatic plug connecting S3 and
  S4(Evidence:Pronase is a proteolytic enzyme specific for
  blocking inactivation
                   For K calculation show the ion
                   transfer




Selectivity to K
by size



                         Energy states for
                         more/less ions
                                             Berneche S & Roux B 2001
                 Explaining phenomenology- the
                 action potential
• Resting potential Σcurrent=0 -> K=Na+Cl -> K>Na
With depolarization Na voltage dependent channels open
   (K not yet), increasing Na threshold: Na=K.
Then Na increase to create depolarization to increase…
   this is the rapid depolarization. Maximal peak= ENa
   (55mV)
Maximal peak isn’t always reached:
K voltage dependent current opens,
Causing hyper-polarization and the
re-polarization and
after-hyperpolarization phases.
                   Explaining phenomenology- the
                   action potential-conductance
• Resting potential G(Na)>G(k) (but I(k) is bigger).
• With depolarization g(na) increases (m gates), if enough for
   I(Na)>I(K) the depolarization will increase G(Na) (m gates) - rapid
   depolarization.
• Then G(k) increase (n gates) and G(Na) decrease(h gate)- re-
   polarization and
   after-hyperpolarization
  (because G(k) decreases
  with delay)-refractory
  period
• Returning to Vm G(Na)
 react faster then G(K)-
Supra normal period)
                   Explaining phenomenology- refractory
                   potential again

• Refractory period depend upon the time constant of gate h-
   at the re polarization period of the action potential gate h is
   closed. Re-polarization and after hyper-polarization will open
   it, but with delay.
  All closed- absolute refractory
  some opened- relative refractory.
                  Accommodation, Depolarization block
                  and anodic break

• True on longer time scale- long depolarization will close
  h gates, elevating threshold.
  If elevated so that no threshold is feasible-
  Depolarization block

• also the opposite-long hyper-polarization will open h
  gates, lowering threshold.
  If lowered so the Vm is above threshold- anodic break
  response.
  What does it means that hyper-polarization can open
  more h gates?
                    Not all h gate are opened at Vm-
                    Inactivation function

• Accomodutions
Effects = fraction of
h gates opened.

What else is this line
Similar to?

In Vm-60% .Why?
                    pronase

• Blocks Na channel inactivation
  how will it effect- the Action Potential?
  refractory period?
  accommodation?
  general information
  transmit?


Method to see only Na activation: pronase
                                 conditioning hyper-polarization
                                 very brief stimulus
               Side note pronase allows viewing Na+
               deactivation

1.   Pronase



         Vm



         INa
                      Oddities

• A second look at the Na current



                                 voltage




                                 current

Now do you understand better
the time constant for h and m?
                    Oddities II-current window

Behavior of H and M gates is
opposing. The depolarization required
for the transition in interleaved. Result-
depolarization window where there’s
constant current
                  Improvement( few examples)

• Azouz 2000- since the h gate in depolarization dependent, a
  slow increase in depolarization will close more h gate then a
  fast increase-> Action potential threshold will be smaller for
  lager depolarization pulse then a slow one. When do we see
  large depolarization pulse- when the input is synchronized.
  Meaning- threshold prefer coincidences

• Naundorf 2006- the m gates are not independent (at least in the
  cortex where they measured, but cooperative- opening one
  increase the likelihood of the other gates to open, making the
  rapid depolarization steeper (as indeed they find) and making
  synchronous input more preferable.
                  Action potential conductance

• Saltatory conductance- only in nodes of renviar.




• Formally- depolarization should be carried from
  dendrite to axon hillock, and then action
  potential should be carried across (myelin
  coated) axon. Actually- from all places to all
  place.

Speed is depend upon myelin and size and
  (locally) upon t & l
                       Action potential conductance is
                       unidirectional

Depolarization spread
passively to both sizes,
but depolarization is
unidirectional- in the
place last AP occur
there is still refractory.




Hyper-polarization will spread passively-how will it effect future activation?
Notice- depolarization will spread passively back to dendrites-
Back propagation
                  The H&H variations-in space

Variations in excitability along the neuron
Axon hillock: lowest threshold:High density of Na+
channels,Voltage gated channels sensitive to near Vr

Nodes of ranvier: many Na+ and leak channels (1000-2000
  chnls/μm2)

And also:
Presynaptic terminals: Voltage sensitive Ca2+ channels
Dendrites: voltage gated Ca2+, K+ and Na+ channels capable of
  producing APs
Action potential propagation
Depolarizatin fades in time and space, action
   potential regenerates.
In the Axon-Salutatory conductance jumping
   between nodes of renviar.




Formally- depolarization should be carried
  dendrite-> axon hillock(action potential)
 ->axon(ranier)->pre synaptic terminal
Actually- from all places to all place.
Speed is depend upon myelin and size and (locally) upon t
  &l
                    Action potential conductance is
                    unidirectional

Depolarization spread
passively to both sizes,
but depolarization is
unidirectional- in the
place last AP occur
there is still refractory.




Notice- depolarization will spread passively back to dendrites-
Back propagation
Part IV- Single neuron computation
                Models of action potential


H&H is a good “conductance model”, but most models are
  simpler: They use “integrate and fire neurons”-
• point neurons (no spatial considerations)
• every input give small depolarization / hyper-polarization -
  excitatory or inhibitory but of costant size(+1 or -1).
• The inputs are summed. The only determining factor is
  above/below threshold(and the threshold is constant)

1.linearly summing all inputs (conductance is passive)
2.threshold impose non linearity t is a low pass filter)= AND & OR
   functions

=>McCullough and Pitts(1943)- This is sufficient to allow any
  computation
                      Integrate and fire models
Simple common model- leak integrate and fire:
Summing input across time: V(t)=Vm+Rm*Ie(1-exp(-t/t
Time difference (isi) between spike is linear to input amplitude



                                                 1
        1           Rm I e  EL  Vreset  
risi =     = t m ln
                     R I  E V         
       tisi        m e        L    th  
                    I&F : What will input integration be
                    dependent upon? integration in time

Two stimuli arrive with a time difference. Will they be united to a
bigger stimulation or be separated? Dependent on t
As t increase, stimuli are less separable

Very brief: low firing rate,
            coincident detection
Prolonged: higher rate, lower sensitivity
                         Problems with I&F

I & F models are DETERMINISTIC- Same input will necessarily
   lead to same firing rate, and all the cell can do is add up inputs
  )not only the AP is “all or none”, the neuron is “all or none”(.


Theoretically, this played a big part in the bottom up approach to
  visual processes- basic features are added up to more complex
  features…

In reality input and threshold ARE NEVER CONSTANT
                     Inadequacy of I&F models
• Problems:
1. No inactivation (or other conductance references)-can be
   imposed on the models

2. Regular firing- if input is same on average , I&F model will
    produce very regular periodic firing rate with constant
    Inter Spike Interval (ISI)


                                                 1
        1           Rm I e  EL  Vreset  
risi =     = t m ln
                    R I  E V         
                                             
       tisi         m e        L    th  



                       Tal & Schwartz 1999
                                                        Tal & Schwartz 1999


3.Nonlinear I-V curve




In reality, neurons have near Gaussian firing rate.
Rate/Noise: for Gaussian =1, for integrate and
    fire ∞, for neuron ~1.2).




                                                      Realistic ISI distribution
                   I&F inadequacy solutions

TYPE I-assume that the neurons ARE DETERMINISTIC therefore
  their only source of variance is the input. Therefore claiming
  that input is naturally Poisson-like (true). Especially true for high
  threshold and small t

Cannot explain why experiment
controlling input give variable results




                      Variable input              Increasing input variance
                      make variable               will broder ISI distribution,
                          firing rate                  Stevens & zador 1997
TYPE II- assuming non deterministic response and
  implementing it by any of the various non linear component
  of the neuron-voltage gated ion channels, channel is
  difference kinetics, differential distribution of channels,
  morphological changes…

      Strong    VS   weaker negative feedback, softky & koch 1993




                                                         Sometimes give good
                                                                  predictions
                     Conductance models
Adding to H&H specific channels known to be found in various cells, or known
    geometry…
Multitude of voltage activated channels:
     • 4 subtypes of voltage activated Ca2+ channels
     • Voltage activated Cl- channels
     • Voltage activated non-selective cation channels
     • Activation in hyperpolarization (h type)
     • Ca2+ activated voltage dependent K+ channel
     • Rapid, inactivating K+ channel (A type)
“Allows complex information processing”


Example: Epilepsy in mutant mice lacking Ka channels
Example of other channels’ importance- Action potential
is not the only spiking mechanism
Burst firing due to Ca firing:
• Exist cells with 2 additional type of channels:
1. T type voltage activated Ca channels (T for transient)- open at very low
   threshold, inactivate fast.
2. L type voltage activated Ca channels (L for long)- open only at higher
   threshold, very very slow de-activation (not inactivation-what is the
   difference?)
=>T open at low threshold (Vm)->inward current->depolarization-> action
   potential (T close)->higher depolarization->L open for long period- chain of
   action potential
(what stops it?)
Burst firing due to Ca firing:
=>T open at low threshold (Vm)->inward current-
  >depolarization-> action potential (T close)->higher
  depolarization->L open for long period- chain of action
  potential
what stops it?
When will it start again?
How are the action potential effected?
• Burst firing due to Ca firing: what will happen at these cells if
  held depolarized?




                    Conclusion- Action potential isn’t everything!
                  Action potential conductance

• Saltatory conductance- only in nodes of renviar.




• Formally- depolarization should be carried from
  dendrite to axon hillock, and then action
  potential should be carried across (myelin
  coated) axon. Actually- from all places to all
  place.
                      Action potential conductance is
                      unidirectional

Depolarization spread passively to
both sizes, but depolarization is
unidirectional- in the place last AP
occur there is still refractory.




  Hyper-polarization will spread passively-how will it effect future activation?
                  The H&H variations-in space

Variations in excitability along the neuron
Axon hillock: lowest threshold:High density of Na+
channels,Voltage gated channels sensitive to near Vr

Nodes of ranvier: many Na+ and leak channels (1000-2000
  chnls/μm2)

And also:
Presynaptic terminals: Voltage sensitive Ca2+ channels
Dendrites: voltage gated Ca2+, K+ and Na+ channels capable of
  producing APs

				
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