Vert Phys PCB3743

Action PotentialFox Chapter 7 pt 2

© T. Houpt, Ph.D.

Action Potential: electrical signaling along axonsNeurons have resting membrane potential (Vm) at -70 mV.

Chemical or electrical stimulation of the neuron can change Vm

Depolarization: Vm becomes more positive -> excitationHyperpolarization: Vm becomes more negative -> inhibition

Change in Vm causes voltage-sensitive ion channels to open.

Change in permeability of membrane to Na+ ion makes Vm move to Equilibrium Potential of Na+ at +50 mV.

Action PotentialElectrical signal is the wave of ions moving in & out of the axon across the membrane (NOT current moving down the length of the axon)

a wave of depolarization spreads down the axon with voltage-sensitive Na+ channels opening, which raises Vm from -70 mV to +50 mV

Slower voltage-sensitive K+ channels open to restore Vm back to resting potential of -70 mV, as action potential passes by.

T

Fox Figure 7.11

Two ways to change the Membrane Potential:

1. Change the concentrations of an ion, e.g. increase extracellular K+ concentrationDoesn’t happen under normal circumstances, because body and neurons maintain constant environment.

2. Change the permeability of the membrane to an ion, which causes the Vm to move closer to Eion.Neuron regulates opening and closing of gated ion channels

Opening and Closing of Na+ and K+ channelsis basis of Action Potential

Distribution of Ions in Mammalian Neurons

! Outside! Inside (mM)! Eion! Permab.

K+! 5! 150! -90! 1.0

Na+! 150! 15! +62! 0.04

Cl-! 125! 10! -62! 0.045

Vm= -70 mV

Change of Permeability leads to change of Vm

! Outside! Inside (mM)! Eion! Permab.

K+! 5! 150! -90! 1.0

Na+! 150! 15! +62! 20

Cl-! 100! 10! -62! 0.045

Vm = +50 mV

dendrites

pre-

syna

ptic

term

inal

axon

cell body

Na+ Na+ Na+

Na+ Na+ Na+ Na+

+ + + + + + + + + + + + + + + + + + + +

+ + + + + + + + + + + + + + + + + + + +- - - - - - - - - - - - - - - - - - - - -

- - - - - - - - - - - - - - - - - - - - -

Membrane Potential of Neuron

Neurotransmitters cause Na+ channels to open and let Na+ into the neuron.

Glu

Na+

Na pump

dendrites

pre-

syna

ptic

term

inal

axon

cell body

Na+ Na+ Na+

Na+ Na+ Na+ Na+

+ + + + + + + + + + + + + + + + + + + +

+ + + + + + + + + + + + + + + + + + + +- - - - - - - - - - - - - - - - - - - - -

- - - - - - - - - - - - - - - - - - - - -

Membrane Potential of Neuron

Neurotransmitters cause Na+ channels to open and let Na+ into the neuron.

Glu

Na+ Na+

Na+

Na pump

(could also be artificial injection of positive current -- anything that raises Vm from -70 mV -> -30mV)

dendrites

pre-

syna

ptic

term

inal

cell body

Na+ Na+ Na+

Na+ Na+ Na++ + + + + + + + + + + + + + + + - - + +

- - - - - - - - - - - - - - - - - + + - -

Membrane Potential of Neuron

When Na+ moves into the neuron, the neuron fires an action potential (a wave of changing potential)

Na+

Na+

exocytosis of transmitter into next synapse

Na+

Na pump - - - - - - - - - - - - - - - - - + + - - + + + + + + + + + + + + + + + + - - + +

Na+

dendrites

pre-

syna

ptic

term

inal

cell body

Na+ Na+ Na+

Na+ Na+ Na+ Na+

+ + + + + + + + + + + + + + + + + + + +

+ + + + + + + + + + + + + + + + + + + +- - - - - - - - - - - - - - - - - - - - -

- - - - - - - - - - - - - - - - - - - - -

Membrane Potential of Neuron

K+ channels and Na+/K+ pump restore balance of ions-> return to -70 mV membrane potential

Na+

Na pump

dendrites

pre-

syna

ptic

term

inal

axon

cell body

Na+ Na+ Na+

Na+ Na+ Na+ Na+

+ + + + + + + + + + + + + + + + + + + +

+ + + + + + + + + + + + + + + + + + + +- - - - - - - - - - - - - - - - - - - - -

- - - - - - - - - - - - - - - - - - - - -

Membrane Potential of Neuron (summary)

Neurotransmitters cause Na+ channels to open and let Na+ into the neuron.

When Na+ moves into the neuron, the neuron fires an action potential (a wave of changing potential)

K+ channels open slowly behind Na+ wave, so neuron returns to -70 mV Vm

Na+/K+ ATPase pump restores balance of ions

Glu

Na+ Na+

exocytosis of transmitter into next synapse

Na+

Na+

Na pump

Summary of Action Potential (AP)

1. Depolarization by electrical stimulation or neurotransmitter

2. Vm rises above AP threshold (depolarization)

3. Voltage-gated Na+ channels open: Vm moves to ENa

4. Rising Vm depolarizes neighboring membrane: AP starts moving down axon (speed depends on cable properties)

5. Voltage-gated Na+ channels inactivate; Voltage-gated K+ channels open; Vm moves to EK

6. Voltage-gated K+ channels close; Vm returns to resting potential

T

Fox Figure 7.19

Fox Figure 7.19

Watching the action potentialgo past:

+

–

+

–

+

–

Fox Figure 7.12

0 mV

-70 mV

+50 mV

time ->

0 mV

-70 mV

+50 mV

time ->

0 mV

-70 mV

+50 mV

time ->

1. 2.

3.

Na+ Channels open, inactivate & close: Vm rises when N+ channels open.threshold to open Na+ channels

Fox Figure 7.19

Action Potential= voltage spike traveling down axon

Fox Figure 7.13

Vm

Fox Figure 7.14

Tetrodotoxin -- blocks voltage-gated Na+ channels

The first recorded cases of tetrodotoxin poisoning were from the logs of Captain James Cook. He recorded his crew eating some local tropic fish (pufferfish), then feeding the remains to the pigs kept on board. The crew experienced numbness and shortness of breath, while the pigs were all found dead the next morning. In hindsight, it is clear that the crew received a mild dose of tetrodotoxin, while the pigs ate the pufferfish body parts that contain most of the toxin, thus killing them.The toxin was first isolated and named in 1909 by Japanese scientist Dr. Yoshizumi Tahara.

1 pufferfish/30 humans

Weight-for-weight, tetrodotoxin is ten times as deadly as the venom of the many-banded krait of Southeast Asia. It is 10 to 100 times as lethal as black widow spider venom (depending upon the species) when administered to mice, and more than 10,000 times deadlier than cyanide. It has the same toxicity as saxitoxin which causes paralytic shellfish poisoning ([both TTX and saxitoxin block the Na+ channel - and both are found in the tissues of pufferfish]) 

Cable Properties of Axons

1. Wider diameter axons have lower resistance, so wave of depolarization spreads faster

Because ions flow more easily to next segment of membrane in wider axons, action potentials move faster down wider axons.

2. Insulated myelinated axons have higher capacitance, so current is not dissipated and travels further

With myelin sheath, charge is conducted to the next gap in the insulation; action potential jumps from one node of Ranvier to the next node very quickly = saltatory (jumping) conduction

T

Cable Properties

Lord Kelvin

TransAtlantic Cable in 1850-60s

http://alexandria.healthlibrary.ca/documents/notes/bom/unit_6/Lec%2024%20Peripheral%20mechanisms.xml

Nerves can have Axons of different diameters: wider axons are faster, because ions flow more easily to next segment of membrane

Speed of Action Potentials

redrawn from http://faculty.washington.edu/chudler/cv.html

copper wire:350 million mph

Cfiber

walk

mile

sprint

A-deltafiber

bicycle

hound

car

cheetah

asian swift

A-betafiber

airplane

400

300

200

100

0

50

A-alphafiber

miles / hour

Fox Figure 7.18

Without myelin sheath, current leaks out of axon & signal dissapates quickly

Fox Figure 7.20

With myelin sheath, charge is conducted to the next gap in the insulation;action potential jumps from one node of Ranvier to the next node very quickly= saltatory (jumping) conduction

Coding Information in Action Potentials

Action Potential is all-or-nothingOnce Vm reaches threshold for opening voltage-sensitive Na+ channels, then neuron fires an action potential

Stimulation encoded as Rate of Firing If Vm is kept above threshold, then neuron fires multiple action potential (but each AP is the same size). So,

duration of firing of APs = duration of stimulation

The stronger the stimulation, the faster the neuron fires AP. So,

frequency of APs = strength of stimulation

Refractory PeriodDuring refractory period, Na+ channels are inactivated and open K+ channels keep Vm negative (keep neuron hyperpolarized). Neuron cannot fire another AP until Na+ channels become active and K+ channels close.

T

Fox Figure 7.15

Fox Figure 7.16

Fox Figure 7.17