2. 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
3. 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).
4. These two solutions have different
concentrations of their ions.
Furthermore, this difference in
concentrations leads to a difference in
charge of the solutions.
This creates a situation whereby one
solution is more positive than the other.
Therefore, positive ions will tend to
gravitate towards the negative solution.
Likewise, negative ions will tend to
gravitate towards the positive solution.
5. 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.
6. 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.
7. 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)
8. 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.
9. In each case, the facilitated diffusion
of sodium into the cell reduces the
resting potential at that spot on the cell
creating an excitatory postsynaptic
potential or EPSP.
If the potential is reduced to the
threshold voltage (about -50 mv in
mammalian neurons), an action
potential is generated in the cell.
10. Historical Figures
Hodgkin and Huxley
won Nobel Prize for
Voltage clamp in
1961
used to identify the ion
species that flowed
during 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 Nehr
won Nobel Prize for
Patch Clamp in 1991
measured ion flow
through individual
channels
shows that each
channel is either in
open or closed
configuration with no
intermediate. The
sum of many
recordings gives you
the shape of sodium
conductance.
11. 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).
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. Action Potential
If depolarization at a spot on the cell reaches
the threshold voltage, the reduced voltage
which opens up hundreds of voltage-gated
sodium channels in that portion of the plasma
membrane.
During the millisecond that the channels
remain open, some 7000 Na+ rush into the
cell. The sudden complete depolarization of the
membrane opens up more of the voltage-gated
sodium channels in adjacent portions of the
membrane.
In this way, a wave of depolarization sweeps
along the cell. This is the action potential (In
neurons, the action potential is also called the
19. 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.
24. • 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
26. Action Potential: a transient and
rapid sequence of changes in
the membrane potential
Action Potentials
Can travel up to
100 meters/second
Usually 10-20 m/s
0.1sec delay between
muscle and sensory
neuron action potential
27. The majority of all action potentials are
generated in the axon hillock. However in
sensory neurons the action potential is
generated by the peripheral (axonal)
process, just proximal to the receptor
region. These areas are also known as
the trigger regions.
An action potential is generated due to
membrane potential reaching threshold
due to a graded potential. Threshold is a
membrane potential at which the
membrane in the trigger region reaches
approximately -55mV, a depolarization of
about 15 mV.
28. 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.
29. 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.
30. 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.
31. 2a) This phase is actually consists of two sub
steps. As the trigger region membrane is
depolarized to threshold voltage, gated
sodium channels begin to open.
By the time threshold potential is reached
enough voltage gated sodium channels are
opened that the potential is now self
generating, being driven on by the influx of
Na+.
With the vast majority of the sodium
channels opened Na+ floods into the cell,
further depolarizing the cell, and increasing
the membranes permeability to sodium by
over 1000 times.
Eventually the cell lets in so many positively
charged sodium ions that the membrane
potential goes from -70mV to +50mV.
32. 2b) As the membrane potential reaches
50mV, and the cell interior becomes more
and more positive, sodium entry becomes
less rapid, as the electrical gradient starts
to repel the ions.
Furthermore in less than a millisecond of
reaching threshold the sodium gates begin
to close.
This additionally causes the membrane to
start to loose permeability with regard to
the sodium ions.
As the net influx of sodium declines, and
then finally stops, the membrane has
reached it’s maximum depolarization at
about +50mV.
33. 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
34. 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.
35. Steps involved
◦ Membrane depolarization and sodium
channel activation
◦ Sodium channel inactivation
◦ Potassium channel activation
◦ Return to normal permeability
36. The mechanism of Action
Potential When membrane Potential
increases
The potassium channel
begins to open slowly
The fast sodium
subunits open rapidly
The slow sodium
channel subunit begins
to close 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
37.
38. 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
40. 6 Characteristics of an Action
Potential
An action potential is initiated at a axon
hillock.
It Triggered by depolarization
a less negative membrane potential that
occurs transiently
Understand depolarization, repolarization
and hyperpolarization
41. 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
42. 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).
43. 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
44. For a given neuron, the amplitude and
the duration of the spike potential is
constant, regardless of the stimulus
45. 5 Reverses Polarity
At peak of action potential the
membrane potential reverses polarity
Becomes positive inside as Called
OVERSHOOT
Return to membrane potential to a
more negative potential than at rest
Called UNDERSHOOT
46. 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
47. 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?
48. 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. This
event takes a couple of seconds and you cannot stop it
in the middle. Once the bowl empties, the flush is
complete. Now the upper tank is empty. If you try pulling
the handle at this point, nothing happens (absolute
refractory). Wait for the upper tank to begin refilling. You
can now flush again, but the intensity of the flushes
increases as the upper tank refills (relative refractory)
49. TIME
VM
In this figure, what do the red
and blue box represent?
50. 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?
51. 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.
52. Continuous Conduction
Occurs in unmyelinated axons.
In this situation, the wave of de- and repolarization
simply travels from one patch of membrane to the
next adjacent
patch.
APs moved
in this fashion
along the
sarcolemma
of a muscle
fiber as well.
Analogous to
dominoes
falling.
53. 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.
54. 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.
55. 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
56. 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.
57. 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.
58. 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.
59. 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?
60. The answer to 1 is a myelinated axon.
If you can’t see why, then answer this
question: could you move 100ft faster
if you walked heel to toe or if you
bounded in a way that there were 3ft in
between your feet with each step?
The answer to 2 is an axon with a large
diameter. If you can’t see why, then
answer this question: could you move
faster if you walked through a hallway
that was 6ft wide or if you walked
through a hallway that was 1ft wide?