Changes in electrical potential,

occurring at the surface of the nerve or

muscle tissue at the moment of

excitation. (The activity produced in an organ,

tissue, or part, such as a nerve cell, as a result of

stimulation.)

Consists of a short duration period of

negativity called the spike potential and

secondary changes in potential called

after-potentials

Resting Membrane Potential

Membrane potential at which neuron

membrane is at rest, ie does not fire

action potential(-70 mV)

The cell membrane acts as a barrier

which prevents the inside solution

(intracellular fluid) from mixing with the

outside solution (extracellular fluid).

These two solutions have differentconcentrations of their ions.Furthermore, this difference inconcentrations leads to a difference incharge of the solutions.

This creates a situation whereby onesolution is more positive than the other.

Therefore, positive ions will tend togravitate towards the negative solution.Likewise, negative ions will tend togravitate towards the positive solution.

The resting potential arises from two

activities:

1. The sodium/potassium ATPase. This

pump pushes only two potassium ions

(K+) into the cell for every three

sodium ions (Na+) it pumps out of the

cell so its activity results in a net loss

of positive charges within the cell.

2. Some potassium channels in the

plasma membrane are "leaky" allowing

a slow facilitated diffusion of K+ out of

the cell.

Ionic Relations in the Cell

The

sodium/potassium

ATPase produces

a concentration of

Na+ outside the cell

that is some 10 times

greater than that

inside the cell

a concentration of K+

inside the cell some

20 times greater than

that outside the cell.

The concentrations of chloride ions (Cl-) and calcium ions (Ca2+) are also maintained at greater levels outside the cell EXCEPT that some intracellular membrane-bounded compartments may also have high concentrations of Ca2+ (green oval)

Depolarization

Certain external stimuli reduce the

charge across the plasma membrane.

A. mechanical stimuli (e.g., stretching,

sound waves) activate mechanically-

gated sodium channels.

B. certain neurotransmitters (e.g.,

acetylcholine) open ligand-gated

sodium channels.

In each case, the facilitated diffusionof sodium into the cell reduces theresting potential at that spot on the cellcreating an excitatory postsynapticpotential or EPSP.

If the potential is reduced to thethreshold voltage (about -50 mv inmammalian neurons), an actionpotential is generated in the cell.

Historical Figures Hodgkin and Huxley

won Nobel Prize forVoltage clamp in1961

used to identify the ionspecies that flowedduring action potential

Clamped Vm at 0mv to remove electric driving force than varied external ion concentration and observed ion efflux during a voltage step

Sakman and Nehrwon Nobel Prize forPatch Clamp in 1991

measured ion flowthrough individualchannels

shows that eachchannel is either inopen or closedconfiguration with nointermediate. Thesum of manyrecordings gives youthe shape of sodiumconductance.

The role of electricity in the nervous systems of animals was first observed in dissected frogs by Luigi Galvani, who studied it from 1791 to 1797.

Scientists of the 19th century studied the propagation of electrical signals in whole nerves (i.e., bundles of neurons) and demonstrated that nervous tissue was made up of cells, instead of an interconnected network of tubes (a reticulum).

Carlo Matteucci followed up Galvani's studies and demonstrated that cell membranes had a voltage across them and could produce direct current.

Emil du Bois-Reymond, who discovered the action potential in 1848.

The conduction velocity of action potentials was first measured in 1850 by du Bois-Reymond's friend, Hermann von Helmholtz.

The 20th century was a golden era for

electrophysiology. In 1902 and again

in 1912, Julius Bernstein advanced

the hypothesis that the action potential

resulted from a change in the

permeability of the axonal membrane

to ions.

Bernstein's hypothesis was confirmed

by Ken Cole and Howard Curtis, who

showed that membrane conductance

increases during an action potential.

In 1907, Louis Lapicque suggested that the action potential was generated as a threshold was crossed

In 1949, Alan Hodgkin and Bernard Katz refined Bernstein's hypothesis by considering that the axonal membrane might have different permeabilities to different ions; in particular, they demonstrated the crucial role of the sodium permeability for the action potential.

Hodgkin and Huxley correlated the

properties of their mathematical model

with discrete ion channels that could

exist in several different states,

including "open", "closed", and

"inactivated". Their hypotheses were

confirmed in the mid-1970s and 1980s

by Erwin Neher and Bert Sakmann,

who developed the technique of patch

clamping to examine the conductance

states of individual ion channels.

In the 21st century, researchers are

beginning to understand the structural

basis for these conductance states

and for the selectivity of channels for

their species of ion,[123] through the

atomic-resolution crystal

structures,[15] fluorescence distance

measurements[124] and cryo-electron

microscopy studies.

Julius Bernstein was also the first to introduce the Nernst equation for resting potential across the membrane; this was generalized by David E. Goldman to the eponymous Goldman equation in 1943.The sodium–potassium pump was identified in 1957 and its properties gradually elucidated, culminating in the determination of its atomic-resolution structure by X-ray crystallography. The crystal structures of related ionic pumps have also been solved, giving a broader view of how these molecular machines work.

Action Potential If depolarization at a spot on the cell reaches

the threshold voltage, the reduced voltagewhich opens up hundreds of voltage-gatedsodium channels in that portion of the plasmamembrane.

During the millisecond that the channelsremain open, some 7000 Na+ rush into thecell. The sudden complete depolarization of themembrane opens up more of the voltage-gatedsodium channels in adjacent portions of themembrane.

In this way, a wave of depolarization sweepsalong the cell. This is the action potential (Inneurons, the action potential is also called thenerve impulse.)

The movement of a signal through the

neuron and its axon is all about ions. An

ion is a charged particle, such as Na+, the

sodium ion. It has a positive charge,

because it is missing one electron. Other

ions, of course, are negatively charged.

Cells have membranes that are made of

lipid molecules (fats), and they prevent

most things from entering or leaving the

cell. But all over a cell membrane are

proteins that stick out on both sides of the

cell membrane. Some of these are ion

channels.

The Generation of an Action

Potential

Figure 12.16.2

The Generation of an Action Potential

The Generation of an Action

Potential

• Resting membrane potential is -

70mV

• triggered when the membrane

potential reaches a threshold

usually -55 MV

• if the graded potential change

exceeds that of threshold –

Action Potential

• Depolarization is the change

from -70mV to +30 mV

• Repolarization is the reversal

from +30 mV back to -70 mV)

Action Potential

action potential = nerve impulse

takes place in two stages: depolarizing phase (more positive) and repolarizing phase (more negative - back toward resting potential)

followed by a hyperpolarizing phase or refractory period in which no new AP

can be generated

rising

overshoot

Falling

undershoot

Action Potentials

Can travel up to

100 meters/second

Usually 10-20 m/s

0.1sec delay between

muscle and sensory

neuron action potential

Action Potential: a transient and

rapid sequence of changes in

the membrane potential

The majority of all action potentials aregenerated in the axon hillock. However insensory neurons the action potential isgenerated by the peripheral (axonal)process, just proximal to the receptorregion. These areas are also known asthe trigger regions.

An action potential is generated due tomembrane potential reaching thresholddue to a graded potential. Threshold is amembrane potential at which themembrane in the trigger region reachesapproximately -55mV, a depolarization ofabout 15 mV.

At this point action potentials become

self propagating. This means that one

action potential automatically triggers

the neghboring membrane areas into

producing an action potential.

Thus once threshold is reached action

potentials always propagate down the

axon to the synaptic or secretory

regions of the axon.

The actual process of the action

potential generation occurs in four

steps, consecutive, but overlapping.

These steps are all opening and/or

closing of ion gates, and subsequent

changes in membrane potentials.

1) The first step is the resting state,

where all active ion channels are

closed. Almost all voltage gated

sodium and potassium gates are

closed.

However some potassium is leaking

out via leakage channels, and even

smaller amounts of sodium are

diffusing in.

2a) This phase is actually consists of two substeps. As the trigger region membrane isdepolarized to threshold voltage, gatedsodium channels begin to open.

By the time threshold potential is reachedenough voltage gated sodium channels areopened that the potential is now selfgenerating, being driven on by the influx ofNa+.

With the vast majority of the sodiumchannels opened Na+ floods into the cell,further depolarizing the cell, and increasingthe membranes permeability to sodium byover 1000 times.

Eventually the cell lets in so many positivelycharged sodium ions that the membranepotential goes from -70mV to +50mV.

2b) As the membrane potential reaches50mV, and the cell interior becomes moreand more positive, sodium entry becomesless rapid, as the electrical gradient startsto repel the ions.

Furthermore in less than a millisecond ofreaching threshold the sodium gates beginto close.

This additionally causes the membrane tostart to loose permeability with regard tothe sodium ions.

As the net influx of sodium declines, andthen finally stops, the membrane hasreached it’s maximum depolarization atabout +50mV.

3) As the membrane potential approaches

+50 mV, voltage gated potassium

channels open and positively charged

potassium ions begin to flow out of the

cell.

This begins to repolarise, the cell by

reducing the excess internal positive

charge and moving the membrane

potential closer to the resting potential.

At this point the cell is basically

impermeable to sodium and very

permeable to potassium which rapidly

flows out of the cell down both it’s

electrical (initially) and chemical

4)Potassium efflux (exiting) continues

past the resting potential of -70 mV due

to the slow closing voltage gated

potassium channels.

This causes a hyperpolarisation known

as undershoot which takes the

membrane potential to around -75mV.

Soon afterward the cell returns to

resting potential via the standard

membrane proteins.

Steps involved

◦ Membrane depolarization and sodium

channel activation

◦ Sodium channel inactivation

◦ Potassium channel activation

◦ Return to normal permeability

The mechanism of Action

Potential When membrane Potential

increases

The fast sodium

subunits open rapidly

The slow sodium

channel subunit begins

to close slowly

The potassium channel

begins to open slowly

The sodium

channels open

Influx of sodium Ions

Further increase of

the membrane

potential

The sodium

channels close

Influx of sodium Ions

Terminate

Efflux of Potassium ions

membrane Potential Decreases

Na+ Channels

They have 2 gates.

◦ At rest, one is

closed (the

activation gate) and

the other is open

(the inactivation

gate).

◦ Suprathreshold

depolarization

affects both of

them.

1

2

3

4 5

6 Characteristics of an Action

Potential

An action potential is initiated at a axonhillock.

It Triggered by depolarization

a less negative membrane potential thatoccurs transiently

Understand depolarization, repolarizationand hyperpolarization

2 Threshold

It require a minimal length of stimulus

intensity and duration.

Threshold depolarization needed to

trigger the action potential

10-20 mV depolarization must occur to

trigger action potential

3 All or None

Are all-or- none event

Amplitude of AP is the same

regardless of whether the depolarizing

event was weak (+20mV) or strong

(+40mV).

4 No Change in Size

Propagates without decrement along axon

The shape (amplitude &

time) of the action

potential does not

change as it travels

along the axon

For a given neuron, the amplitude and

the duration of the spike potential is

constant, regardless of the stimulus

5 Reverses Polarity

At peak of action potential themembrane potential reverses polarity

Becomes positive inside as CalledOVERSHOOT

Return to membrane potential to amore negative potential than at restCalled UNDERSHOOT

6 Refractory Period

Absolute refractory period follows an

action potential. Lasts 1 msec

During this time another action

potential CANNOT be fired even if

there is a transient depolarization.

Limits firing rate to 1000AP/sec

Absolute Refractory Period

During the time interval between the

opening of the Na+ channel activation gate

and the opening of the inactivation gate, a

Na+ channel CANNOT be stimulated.

◦ This is the ABSOLUTE REFRACTORY PERIOD.

◦ A Na+ channel cannot be involved in another AP

until the inactivation gate has been reset.

◦ This being said, can you determine why an AP is

said to be unidirectional.

What are the advantages of such a scenario?

Relative Refractory Period

Could an AP be generated during the undershoot?

Yes! But it would take an initial stimulus that is

much, much stronger than usual.

WHY?

This situation is known as the relative refractory

period.

Imagine, if you will, a toilet.

When you pull the handle, water floods the bowl. Thisevent takes a couple of seconds and you cannot stop itin the middle. Once the bowl empties, the flush iscomplete. Now the upper tank is empty. If you try pullingthe handle at this point, nothing happens (absoluterefractory). Wait for the upper tank to begin refilling. Youcan now flush again, but the intensity of the flushesincreases as the upper tank refills (relative refractory)

TIME

VM

In this figure, what do the red

and blue box represent?

Some Action Potential Questions

What does it mean when we say an

AP is “all or none?”

◦ Can you ever have ½ an AP?

How does the concept of threshold

relate to the “all or none” notion?

Will one AP ever be bigger than

another?

◦ Why or why not?

Action Potential Conduction

If an AP is generated at the axon hillock, it

will travel all the way down to the synaptic

knob.

The manner in which it travels depends on

whether the neuron is myelinated or

unmyelinated.

Unmyelinated neurons undergo the

continuous conduction of an AP whereas

myelinated neurons undergo saltatory

conduction of an AP.

Continuous Conduction Occurs in unmyelinated axons.

In this situation, the wave of de- and repolarizationsimply travels from one patch of membrane to the next adjacent patch.

APs moved in this fashion along the sarcolemmaof a muscle fiber as well.

Analogous to dominoes falling.

Saltatory Conduction

Occurs in myelinated axons.

Saltare is a Latin word meaning “to leap.”

Recall that the myelin sheath is not completed. There

exist myelin free regions along the axon, the nodes of

Ranvier.

The myelin sheath around many

axons speeds up this process

considerably: Instead of one tiny

segment triggering action at the very

next little segment, the changes

"jump" from one gap in the sheath to

the next. This is called saltatory

conduction.

The evolutionary need for the fast and

efficient transduction of electrical

signals in nervous system resulted in

appearance of myelin sheaths around

neuronal axons.

Myelin is a multilamellar membrane

which enwraps the axon in segments

separated by intervals known as

nodes of Ranvier, is produced by

specialized cells, Schwann cells

exclusively in the peripheral nervous

system, and by oligodendrocytes

exclusively in the central nervous

Myelin sheath reduces membrane

capacitance and increases membrane

resistance in the inter-node intervals,

thus allowing a fast, saltatory

movement of action potentials from

node to node.

Myelin prevents ions from entering or

leaving the axon along myelinated

segments.

As a general rule, myelination

increases the conduction velocity of

action potentials and makes them

more energy-efficient.

Whether saltatory or not, the mean

conduction velocity of an action

potential ranges from 1 m/s to over

100 m/s, and generally increases with

axonal diameter.

Although the mechanism of saltatory

conduction was suggested in 1925 by

Ralph Lillie.

The first experimental evidence for

saltatory conduction came from Ichiji

Tasaki-1968, Taiji Takeuchi-1969 and

from Andrew Huxley and Robert

Stämpfli-1970.

Rates of AP Conduction

1. Which do you think has a faster rate of AP

conduction – myelinated or unmyelinated

axons?

2. Which do you think would conduct an AP

faster – an axon with a large diameter or an

axon with a small diameter?

The answer to 1 is a myelinated axon.If you can’t see why, then answer thisquestion: could you move 100ft fasterif you walked heel to toe or if youbounded in a way that there were 3ft inbetween your feet with each step?

The answer to 2 is an axon with a largediameter. If you can’t see why, thenanswer this question: could you movefaster if you walked through a hallwaythat was 6ft wide or if you walkedthrough a hallway that was 1ft wide?