biopsych slide 4

7/17/2019 Biopsych Slide 4

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Psy 111 Basic concepts in Biopsychology

L 4 Th A i P i lecture 4: The Action Potential


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Electrochemical Equilibrium &

Nernst Equation

=

on ou s ez [ion] inside

For K+,on outside = m

& [ion]inside = 100 mM

EK+ = -80mV.

For Na+,[ion]outside = 150 mM

& [ion]inside = 15 mM

K+ = .


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Resting Membrane Potential Summary

Ion out in Ratio EionK+ 5 mM 100 mM 1:20 -80 mV

Na+

150 mM 15 mM 10:1 62 mVCl - 150 mM 13 mM 11.5:1 -65 mV

Vm= (61.54) log PK[K

+

0]out + PNa [Na

+

]out + PCl [Cl

-

]out+ + -

K in Na in Cl in

t rest, mem rane as a arge re at ve permea tyto K+ versus Na+

For our purposes: there is a population of K+ channels that are

always open i.e. non-gated


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Membrane Potentials in Excitable Cells

50He atoc te

Recordings from

0Vm

-50

Today we focus

50Neuron

on what is

happening

0

-50

Vm

membrane is

active!

2 mSec


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Objectives

Describe the electrical properties of excitable membranes.

escr e e proper es an s ages o e ac on po en a .

Define generator potential and threshold and the relationbetween the two including the relation between magnitude of

generator potent a an magn tu e o neurona response.

Discuss relation of changes in membrane potential and

relative permeability of K+:Na+ during the stages of theaction potential.

Identify the voltage gated channels involved in the action

potential and the properties of these channels.

Describe relation between vg-Na+ channels and voltagesensitivity.

Describe the positive feedback in generation of action

potentials.

Discuss role of vg-Na+ channel inactivation in conduction ofaction potentials.


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The Action Potential

1. Properties and description.

3. Ion channels & gating. on uct on


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Description of AP stages

2 mSec

2 mSec


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Properties and description of the AP

AP Generation requires input = Generator Potential

can be experimentally induced as depicted.


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Generator potential must be of threshold value to generate AP

Larger generator potentials increase frequency (not size) of APs


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Increasing Generator potential increase AP frequency-due to transient Relative refractoriness;

a.ka. Relative refractory period.

Frequency can be increased only to maximum ~1000/Sec.

-due to transient Absolute refractoriness

a.k.a. Absolute refractory period


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Falling phase or

corresponds to

absolute refractoryper o

hyperpolarization

corresponds to relative

re rac ory per o


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3. Ion channels & gating. on uct on


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APs, Relative Permeabilites, & Currents

Vm = (61.54) log PK[K+0]out + PNa [Na

+]out+ +

K in Na in


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Rising Phase.

Opening extra Na+ channels

e a ve ermea y

K+ Na+

Rest 40 1

Rise 40 400Fall 100 1

est


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Fallin Phase Inc. rel perm of K+ Closing extra Na+ channels

e a ve ermea y

K+ Na+

Rest 40 1Rise 40 400

Fall 100 1Rest 40 1


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Relative Permeability

Dynamics in an AP.

e a ve ermea y

K+ Na+

Rest 40 1

Rise 40 400

Fall 100 1Rest 40 1


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3. Ion channels & gating

. on uct on


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Ion Channels mediating APs

Two types of voltage-gated ion channels mediate

potentialInactivatin Volta e- ated Na+ Channel

Delayed (Rectifying) Voltage-gated K+ Channel

Gated channels are those that

un ergo c anges n t eprobability of being open or

closed resultin in chan es in

relative permeablity of the

membrane to specific ions.


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Ion Channels

structurally and functionally

similar proteins.

Form a pore a ow ng ons tomove across membrane

Com rised of membrane-

spanning domains (either one

polypeptide or separate subunits).


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vg-Na+ Channels

InactivatingVoltage-gated Na+

anne

single polypeptide

6 transmembrane

spans/domains

voltage-sensitiveselective pore

nact vat on gate


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vg-Na+ channels

+

depolarization

Inactivating Voltage-gated Na+ Channel

voltage-sensitive activation of selective pore

is due to modest depolarization


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Selective Pores

Na+fits

Na+ vs. K+ ions:

Equal chargeDifferent hydrated sizes

allows Na+ selective pore.


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vg-Na+ Channels

Inactivating

Voltage-gated Na+

-voltage-sensitive

activation gate

- nac va on ga e

Removal o inactivation occurs onl when

membrane repolarizes (ie at~-65mV)

Thus, vg-Na+ channel inactivation mediates absolute refractory period becauseneed to return to RMP to remove and this limits the maximal rate of firing.


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vg-Na+ channels: Blockade.

Local anesthetics block Na+ channels

(e.g., lidocaine, cocaine, procaine)

Produces reversible lesion by preventing

depolarization results in blockade of

action potentials i.e. no rising phase is

possible.

no action potentialsno conductance of

pain information

Note: the interaction between hydrogens

on lidocaine and the receptor site on the

+

Waals forces


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vg-Na+ channels: Blockade.

etro o to x n rom pu er s orfugu

Produces very potent reversible lesion;

10 times more poisonous than cyanide.

Other natural toxins also impact the

.


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vg-K+ channels

Delayed (Rectifying)

Voltage-gated K+

Channelfour polypeptides

our su un s

6 transmembrane

s ans/domainsvoltage-sensitive

slow activation

se ec ve pore +depolarization

g- + c anne a so s ow o c ose w c me a es re a ve re ac ory per o

i.e. higher than at rest K+ permeability therefore need greater generator

potential for AP.


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vg-K+ channels

Selective ore as for non- ated K+

channelSimilar vg mechanism as vg-Na+


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Ion Channels during APsRest:

ng-K+ channels open

vg-Na+ channels closed

vg-K+ channels -closed

Rise:

ng-K+ channels open

vg-Na+ channels open

vg-K+ channels -closed

Fall:-

vg-Na+ channels inactivate

vg-K+ channels open

ng-K+ channels openvg-Na+ channels reset/closed

v -K+ channels close

Inactivation is critical for spatial aspects of the

AP: conduction from one place to another


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3. Ion channels & gating

. on uct on


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Conduction of the Action Potential-movement of AP from place to place along the membrane.

i. AP Generation inthe axon hillock

with a squid:

. AP on uct on

down the axon

iii. Conduction velocityand myelination


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Generation of AP in Axon Hillock

Axon Hillock (Initial Segment)-high in vg Na+ Channels

-high sensitivity (relative to

dendrites & cell body) to generator

po en a s

-amplifies generator potential


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Generation of AP in Axon Hillock

Generator

Potential

axon hillock

Act like a domino effect


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Generation and conduction of APs

Density of voltage-gated Na+ channels determines sensitivity to depolarization

Allows generation of AP (hillock)

Conduction of AP (axon)

I Ch l & Mi di t


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Ions, Channels, & Microgradientse. . Na+ channels

1. Channel Closed

(at rest)

2. Channel Opens

3. Channel Closes

(ions diffuses)

Botton (Inside) ViewSide View

AP G i d C d i


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AP Generation and Conduction

Na+

Soma Hillock Axon

Na+

Soma Hillock Axon

Na +Na +

GeneratorPotential

X = inactivation gate

But why does it go in one direction?


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Conduction of AP down Axon

Again, goes in one direction due to inactivation gate on proximal

(toward soma) side of axon


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Conduction Speed

Speed is determined by conductance which is

propor ona o vo ume, arger s as er an ess ea age

(i.e. surface area versus volume).


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Myelination: speeds up electrical signalSaltatory conduction: jumping of electrical signal from node to node

Node of Ranvier

C d i S d


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Conduction Speed

Myelin serves to insulate axon:

reduces leakage->stronger repulsion down axon->faster conduction

Disorder affecting myelination:


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Disorder affecting myelination:

Multi le Sclerosis MS characterized by the degeneration of myelin, resulting in neuronal death and the

formation of plaques (hardenings) in brain and spinal cord

Disru tion in fast saltator conductance sometimes loss of conductance

altogether

Results in weakness, paralysis or spasms, impaired coordination, visual problems

etc.

White=myelin=axons

An auto-immune disease where your bodyis attacking its own myelin

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