Science Brain and Behavior contiuned 13

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HOW DO NEURONS TRANSMIT INFORMATION? ! 121
(D) Charge
(A) Resting potentisl
Axon
0
Axon
–70
Time (ms)
Voltage (mV)
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
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–
+
–
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–
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–
+
–
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–
+
–
+
–
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + +
–
– – – – – – – – – – – – – – – – – – – – – – – – – – –
(B) Ion distribution
(C) Channels and pumps
A– ions and K+ ions have
higher concentration
inside axon relative to
outside,...
…whereas Cl– ions
and Na+ ions are
more concentrated
outside the axon.
K+
K+
Extracellular
fluid
Intracellular
Intracellular fluid
Extracellular
3 Na+
A– K+ Na+ Cl–
2 K+
Na+
A–
Na+ channels are
ordinarily closed to
prevent entry of Na+.
K+ is free to
enter and leave
the cell.
Na+–K+ pumps
out three Na+
for two K+.
Unequal distribution of
different ions causes inside of
axon to be relatively negatively
charged.
One electrode
records outer
surface of
axon…
…while another
records inner surface.
By convention, extracellular
side of membrane is given
a charge of 0 mV;…
…therefore intracellular
side of membrane is –70 mV
relative to extracellular side.
This is the membrane’s
resting potential.
Figure 4-10
Resting Potential The electrical charge
across a cell membrane produced by
differences in ion concentration.
ELECTRICAL ACTIVITY OF A MEMBRANE
Specific aspects of the cell membrane’s electrical activity interact to convey information
throughout the nervous system. The movement of ions across neural membranes
creates the electrical activity that enables this information to flow.
Resting Potential
Figure 4-10A graphs the voltage difference recorded when one microelectrode is placed
on the outer surface of an axon’s membrane and another is placed on its inner surface.
In the absence of stimulation, the difference is about 70 mV.Although the charge on the
In Review .
Even several hundred years ago, experimental results implicated electrical activity in the
nervous system’s flow of information. But not until the mid–twentieth century did scientists
solve all the technical problems in measuring the changes in electrical charge that
travel like a wave along an axon’s membrane. Their solutions included recording from the
giant axons of the North Atlantic squid, using an oscilloscope to measure small changes
in voltage and obtaining microelectrodes small enough to place on or into an axon. The
electrical activity of axons entails the diffusion of ions that move both down a concentration
gradient (from an area of relatively high concentration to an area of lower concentration)
and down a voltage gradient (from an area of relatively high charge to an area of
lower charge). The flow of ions in the nervous system is also affected by the semipermeable
membrane and ion channels in cell membranes, which may open (facilitating ion
movement), close (impeding that movement), or pump ions across the membrane.
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outside of the membrane is actually positive, by convention it is given a charge of zero.
Therefore, the inside of the membrane at rest is !70 mV relative to the extracellular side.
If we were to continue to record for a long period of time, the charge across the
membrane would remain much the same. The difference in charge on the inside and
outside of the membrane creates an electrical potential; however, the charge can
change, given certain changes in the membrane. The charge is thus a store of potential
energy called the membrane’s resting potential. (We might use the term potential in
the same way to talk about the financial potential of someone who has money in the
bank—that person can spend that money at some future time.)
The resting potential, then, is a store of energy that can be used at a later time.Most
of your body’s cells have a resting potential, but it is not identical on every axon.A resting
potential can vary from !40 to !90 mV on axons of different animal species.
Four charged particles take part in producing the resting potential: ions of sodium
(Na") and potassium (K"), chloride ions (Cl!), and large protein molecules (A!). As
Figure 4-10B shows, these charged particles are distributed unequally across the axon’s
membrane, with more protein anions and K" ions in the intracellular fluid and more
Cl! and Na" ions in the extracellular fluid. Let us consider how the unequal concentrations
arise and how each contributes to the membrane’s resting potential.
Large protein anions are manufactured inside cells.No membrane channels are large
enough to allow these proteins to leave the cell; so they remain in the intracellular fluid,
and their charge contributes to the negative charge on the inside of the cell membrane.
The negative charge of protein anions alone is sufficient to produce a transmembrane
voltage or resting potential. Because most cells in the body manufacture these large, negatively
charged protein molecules,most cells have a charge across the cell membrane.
To balance the negative charge created by large protein anions in the intracellular
fluid, cells accumulate positively charged K" ions to the extent that about 20 times as
many potassium ions cluster inside the cell as outside it. Potassium ions cross the cell
membrane through open potassium ion channels, as shown in Figure 4-10C.With this
high concentration of potassium ions inside the cell, however, the potassium ion concentration
gradient across the membrane limits the number of K" ions entering the
cell. In other words, some potassium ions do not enter the cell, because the internal
concentration of K" ions is much higher than the external K" concentration.
A few residual K" ions are enough to contribute to the charge across the membrane,
adding to the negativity on the intracellular side of the membrane relative to the
extracellular side. You may be wondering whether you read the last sentence correctly.
If there are 20 times as many positively charged potassium ions inside the cell as there
are outside, why should the inside of the membrane have a negative charge? Should not
all those K" ions in the intracellular fluid give the inside of the cell a positive charge
instead? No, because not quite enough potassium ions are able to enter the cell to balance
the negative charge of the protein anions.
Think of it this way: if the number of potassium ions that could accumulate on the
intracellular side of the membrane were unrestricted, the positively charged potassium
ions inside would exactly match the negative charges on the intracellular protein anions.
There would be no charge across the membrane at all. But there is a limit on the
number of K" ions that accumulate inside the cell because, when the intracellular
potassium ion concentration becomes higher than the extracellular concentration, further
K" influx is opposed by the potassium concentration gradient.
The equilibrium of the potassium voltage gradient and the potassium concentration
gradient results in some potassium ions remaining outside the cell. Only a few
potassium ions staying outside the cell are needed to maintain a negative charge on the
inner side of the membrane.As a result, potassium ions contribute to the charge across
the membrane.
122 ! CHAPTER 4
On the Foundations CD, visit the
section on the membrane potential in the
module on neural communication. Here
you can view an animation of resting
potential. Note that the oscilloscope
changes in electrical potential when the
cell is stimulated.
Resting potential. Electrical charge
across the cell membrane in the absence
of stimulation; a store of energy produced
by a greater negative charge on the
intracellular side relative to the
extracellular side.
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Recall that sodium (Na") and chloride (Cl!) ions also take part in producing the
resting potential. If positively charged sodium ions were free to move across the membrane,
they would diffuse into the cell and eliminate the transmembrane charge produced
by the unequal distribution of potassium ions inside and outside the cell. This
diffusion does not happen, because sodium ion channels on the cell membrane are ordinarily
closed (see Figure 4-10C), blocking the entry of most sodium ions. Still, given
enough time, sufficient sodium could leak into the cell to neutralize its membrane potential.
The cell membrane has a different mechanism to prevent this neutralization
from happening.
When Na" ions do leak into the neuron, they are immediately escorted out again by
the action of a sodium–potassium pump, a protein molecule embedded in the cell membrane
(see Figure 4-10C). A membrane’s many thousands of pumps continually exchange
three intracellular Na" ions for two K" ions. The K" ions are free to leave the cell
through open potassium channels, but closed sodium channels slow the reentry of the
Na" ions. In this way, Na" ions are kept out to the extent that about 10 times as many
sodium ions reside on the extracellular side of the axon membrane as on the membrane’s
intracellular side. The difference in Na" concentrations also contributes to the resting
potential of the membrane.
Now consider the chloride ions. Unlike sodium ions, Cl! ions move in and out of
the cell through open channels in the membrane. The equilibrium at which the chloride
concentration gradient equals the chloride voltage gradient is approximately the
same as the membrane’s resting potential, and so chloride ions ordinarily contribute
little to the resting potential. At this equilibrium point, there are about 12 times as
many Cl! ions outside the cell as inside it.
As summarized in Figure 4-10D, the unequal distribution of anions and cations
leaves a neuron’s intracellular fluid negatively charged at about !70 mV relative to the
fluid outside the cell. Three aspects of the semipermeable cell membrane contribute to
this resting potential:
1. Large negatively charged protein molecules remain inside the cell.
2. Gates keep out positively charged Na" ions, and channels allow K" and Cl! ions
to pass more freely.
3. Na"–K" pumps extrude Na" from the intracellular fluid.
Graded Potentials
Recall that the charges on the inside and the outside of the cell membrane can change.
If the concentration of any of the ions across the cell membrane changes, the membrane
voltage will change. The resting potential provides an energy store that can be
used somewhat like the water in a dam, where small amounts can be released by opening
gates for irrigation or to generate electricity.
Conditions under which ion concentrations across the cell membrane change produce
graded potentials, relatively small voltage fluctuations that are restricted to the
vicinity on the axon where ion concentrations change. Just as a small wave produced
in the middle of a large, smooth pond decays before traveling much distance, graded
potentials produced on a membrane decay before traveling very far. But an isolated
axon will not undergo a spontaneous change in charge. For a graded potential to arise,
an axon must somehow be stimulated.
Stimulating an axon electrically through a microelectrode mimics the way in which
the membrane voltage changes to produce a graded potential in the living cell. If the voltage
applied to the inside of the membrane is negative, the membrane potential increases
HOW DO NEURONS TRANSMIT INFORMATION? ! 123
3 Na+
Sodium–potassium pump
Intracellular
fluid
Extracellular
fluid
2 K+
Graded potential. Small voltage
fluctuation in the cell membrane estricted
to the vicinity on the axon where ion
concentrations change to cause a brief
increase (hyperpolarization) or decrease
(depolarization) in electrical charge
across the cell membrane.
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124 ! CHAPTER 4
Hyperpolarization. Increase in
electrical charge across a membrane,
usually due to the inward flow of
chloride ions or the outward flow of
potassium ions.
Depolarization. Decrease in electrical
charge across a membrane, usually due
to the inward flow of sodium ions.
Action potential. Large, brief, reversal
in polarity of an axon.
Threshold potential. Voltage on a
neural membrane at which an action
potential is triggered by the opening of
Na" and K" voltage-sensitive channels;
about !50 millivolts relative to
extracellular surround.
Voltage-sensitive channel. Gated
protein channel that opens or closes only
at specific membrane voltages.
Figure 4-11
Graded Potentials (A) Stimulation (S)
that increases relative membrane
voltage produces a hyperpolarizing
graded potential. (B) Stimulation that
decreases relative membrane voltage
produces a depolarizing graded
potential.
in negative charge by a few millivolts.As illustrated in Figure 4-11A, it may change from
a resting potential of !70 mV to a new, slightly greater potential of !73 mV.
This change is a hyperpolarization because the charge (polarity) of the membrane
increases. Conversely, if positive voltage is applied inside the membrane, its potential
decreases by a few millivolts. As illustrated in Figure 4-11B, it may change from a resting
potential of !70 mV to a new, slightly smaller potential of !65 mV. This change
is a depolarization because the membrane charge decreases. Graded potentials are
usually brief, lasting only milliseconds.
Hyperpolarization and depolarization typically occur on the soma (cell-body)
membrane and on the dendrites of neurons. These areas contain channels that can
open and close, causing the membrane potential to change (see Figure 4-11). Three
channels, for sodium, potassium, and chloride ions, underlie graded potentials.
For the membrane to become hyperpolarized, its extracellular side must become
more positive, which can be accomplished with an efflux of K" ions or an influx of Cl!
ions. Evidence that potassium channels have a role in hyperpolarization comes from
the fact that the chemical tetraethylammonium (TEA), which blocks potassium channels,
also blocks hyperpolarization. But, if potassium channels are ordinarily open, how
can a greater-than-normal efflux of K" ions take place? Apparently, even though potassium
channels are open, there is still some resistance to the outward flow of potassium
ions. Reducing this resistance enables hyperpolarization.
Depolarization, on the other hand, can be produced by
an influx of sodium ions and is produced by the opening
of normally closed sodium channels. The involvement of
sodium channels in depolarization is indicated by the fact
that the chemical tetrodotoxin, which blocks sodium channels,
also blocks depolarization. The puffer fish, which is
considered a delicacy in some countries, Puffer fish especially Japan,
0
–70
–73
S
Time (ms)
Voltage (mV)
(A) Hyperpolarization
Cl–
Intracellular fluid
S
0
Time (ms)
Voltage (mV)
(B) Depolarization
Extracellular fluid
–70
–65
K+
Intracellular fluid
Extracellular fluid
Na+
Hyperpolarization is due to
an efflux of K+, making the
extracellular side of the
membrane more positive.
An influx of Cl– also can
produce hyperpolarization.
Neuron axon
Depolarization is
due to an influx
of Na+ through
Na+ channels.
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secretes this potentially deadly poison; so skill is required to prepare this fish for dinner.
The fish is lethal to the guests of careless cooks because its toxin impedes the electrical
activity of neurons.
The Action Potential
An action potential is a brief but extremely large reversal in the polarity of an axon’s
membrane that lasts about 1 ms. Figure 4-12A illustrates the magnitude of the voltage
change associated with an action potential. The voltage across the membrane suddenly
reverses, making the intracellular side positive relative to the extracellular side, and
then abruptly reverses again, after which the resting potential is restored. Because the
duration of the action potential is so brief, many action potentials can occur within a
second, as illustrated in Figure 4-12B and C, where the time scales are compressed. An
action potential occurs when a large concentration of first Na" ions and then K" ions
cross the membrane rapidly.
The change in membrane polarity that underlies an action potential occurs only
when electrical stimulation causes the membrane potential to drop to about !50 mV
relative to the charge outside the membrane.At this voltage level, or threshold potential,
the membrane undergoes a remarkable further change in charge with no additional
stimulation. The relative voltage of the membrane drops to zero and then continues to
depolarize until the charge on the inside of the membrane is as great as "30 mV—a total
voltage change of 100 mV. Then the membrane potential reverses again, becoming
slightly hyperpolarized—a reversal of a little more than 100 mV. After this second reversal,
the membrane slowly returns to its resting potential.
Experimental results reveal that the voltage that produces an action potential is
due to a brief influx of sodium ions followed by a brief efflux of potassium ions. If an
axon membrane is stimulated to produce an action potential while the solution
surrounding the axon contains TEA (to block potassium channels), a smaller-thannormal
action potential due entirely to a sodium influx is recorded. Similarly, if an
axon’s membrane is stimulated to produce an action potential while the solution surrounding
the axon contains tetrodotoxin (to block sodium channels), a slightly different
action potential due entirely to the efflux of potassium is recorded. Figure 4-13
illustrates these experimental results, showing that the action potential on an axon normally
consists of the summed current changes caused first by the inflow of sodium and
then by the outflow potassium ions.
THE ROLE OF VOLTAGE-SENSITIVE ION CHANNELS
What cellular mechanisms underlie the movement of Na" and K" ions to produce an action
potential? The answer lies in the behavior of a class of sodium and potassium ion
channels that are sensitive to the membrane’s voltage. These voltage-sensitive channels
HOW DO NEURONS TRANSMIT INFORMATION? ! 125
Voltage (mV)
–70
Time (ms)
1 2 3
Time (ms)
20 30
(B)
Voltage (mV)
–70
(C)
–50
Voltage (mV)
0
30
–70
–100
Time (ms)
Threshold
1 2
(A) Action potential
10
Figure 4-12
Measuring Action Potentials The time
scale on the horizontal axis compresses
to chart (A) the phases of a single action
potential, (B) each action potential as a
discrete event, and (C) the ability of a
membrane to produce many action
potentials in a short time.
!50 mV
K+ channel
K+
Voltage-sensitive
potassium channel
K+ Intracellular
fluid
Extracellular
fluid
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126 ! CHAPTER 4
are closed when an axon’s membrane is at its resting potential, and so ions cannot pass
through them.When the membrane reaches threshold voltage, the configuration of the
voltage-sensitive channels alters, enabling them to open and let ions pass through them.
Thus, these “gated” channels can open to permit the flow of ions or close to restrict the
flow of ions.
Voltage-sensitive channels are attuned to the threshold voltage of !50 mV.Voltagesensitive
sodium channels are more sensitive than the potassium channels, and so the
voltage change due to sodium ion influx occurs slightly before the voltage change due
to potassium ion efflux. “Opening the Voltage-Sensitive Gates” explains current thinking
about how gated channels work and how they evolved.
ACTION POTENTIALS AND REFRACTORY PERIODS
Although action potentials can occur as many as hundreds of times a second, their frequency
has an upper limit. If the axon membrane is stimulated during the depolarizing
phase of the action potential, another action potential will not occur. The axon will also
not produce another action potential when it is repolarizing, or absolutely refractory.
(Exceptions do exist: some CNS neurons can discharge again during the repolarizing
phase.)
If, on the other hand, the axon membrane is stimulated during hyperpolarization,
another action potential can be induced, but the stimulation must be more intense
than that which initiated the first action potential. During this phase, the membrane is
relatively refractory. Because of refractory periods, there is about a 5-ms limit on how
frequently action potentials can occur. In other words, an axon can produce action potentials
at a maximum rate of about 200 per second.
Refractory periods are due to the way that gates of the voltage-sensitive sodium and
potassium channels open and close. Sodium channels have two gates, and potassium
Absolutely refractory. Refers to the
state of an axon in the repolarizing
period during which a new action
potential cannot be elicited (with some
exceptions), because gate 2 of sodium
channels, which is not voltage-sensitive,
is closed.
Relatively refractory. Refers to the
state of an axon in the later phase of an
action potential during which increased
electrical current is required to produce
another action potential; a phase during
which potassium channels are still open.
Time (ms)
(C)
Na+ + K+
0 1 2 3 4
–20
–80
0
20
–60
–40
Na+
K+
TEA
Na+
K+
K+
K+
K+
Tetrodotoxin
Extracellular
fluid
Neuron axon
Intracellular fluid
Na+
Na+
Na+ influx
Time (ms)
K+ efflux
0 1 2 3 4
Voltage (mV)
An action potential is produced by changes in
voltage-sensitive K+ and Na+ channels, which can
be blocked by TEA and tetrotoxin, respectively.
…results in a normal action
potential that consists of the
summed voltage changes due to
Na+ and K+.
(A) (B)
The opening of Na+ channels produces a Na+ influx.
Na+
The combined influx of
Na+ and efflux of K+…
The opening of K+ channels produces a K+ efflux.
Figure 4-13
Physiology of the Action Potential
Experiments demonstrate that the action
potential on an axon results from an
inward flow of sodium ions followed by
an outward flow of potassium ions.
You can use the Foundations CD to
review the action potential animation
described on page 119. Note the ionic
changes associated with this phenomenon
and the oscilloscope readout for the action
potential.
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HOW DO NEURONS TRANSMIT INFORMATION? ! 127
channels have one gate. Figure 4-14 illustrates the position of these gates before, during,
and after the various phases of the action potential.
During the resting potential, gate 1 of the sodium channel depicted in Figure 4-14
is closed and only gate 2 is open.At the threshold level of stimulation, gate 1 also opens.
Gate 2, however, closes very quickly after gate 1 opens. This sequence produces a brief
period during which both gates are open followed by a brief period during which gate
2 is closed.When gate 1 opens, the membrane depolarizes and, when gate 2 closes, depolarization
ends. The opening of the K" channels repolarizes and eventually hyperpolarizes
the membrane.
Both sodium gates eventually regain their resting potential positions, with gate 1
closed and gate 2 open. But, while gate 2 of the Na" channel is closed, the membrane
is absolutely refractory. Because the potassium channels close more slowly than the
sodium channels do, the hyperpolarization produced by a continuing efflux of potassium
ions makes the membrane relatively refractory for a period of time after the action
potential has passed. The refractory periods have very practical uses in conducting
information, as you will see next, when we consider the nerve impulse.
A lever-activated toilet provides an analogy for some of the changes in polarity that
take place during an action potential. Pushing the lever slightly produces a slight flow of
Opening the Voltage-Sensitive Gates
Focus on New Research
The cell membrane is studded with ion channels that regulate
the transport of sodium, potassium, and calcium ions
into and out of the cell. Each of these complex proteins contains
a pore (channel) through which an appropriate ion can
pass. Some ion channels also have a voltage-sensitive structure
(a gate) that opens in response to changes in the cellmembrane
voltage.
All voltage-sensitive channels (Na", Ca2", K") have a
similar structure, suggesting that they all have a common origin
but evolved to specialize for allowing different ions to
cross the cell membrane. Potassium voltage-sensitive channels
consist of four protein subunits, with six membrane-spanning
regions. One of them, region 4, is positively charged.
Youxing Jiang and his colleagues (2003) modeled a
potassium voltage-sensitive channel, shown in the accompanying
diagram. Their goal was to understand how its pore
opens in response to voltage changes on the membrane.
They suggested that transmembrane region 4 twists, with a
movement like that of a canoe paddle, in response to membrane-
voltage changes to thus open the pore.
Until recently researchers hypothesized that voltagesensitive
sodium, potassium, and calcium channels are
unique to organisms that have a nervous system, where they
play a role in electrical signaling in neurons. Vanessa Ruta
and her colleagues (2003) found that an archaebacterium
(ancient bacterium) from a deep oceanic thermal vent also
has voltage-sensitive potassium channels. Both the archaebacterium‘
s and the neuron’s voltage-sensitive potassium
channels are affected in the same way by two neurotoxins.
Scorpion venom blocks the voltage sensor, and tarantula
toxin blocks the pore. Because archaebacteria do not have
nervous systems and are located far from scorpions and
tarantulas, voltage channels that play a general role in transmembrane
transportation must have been co-opted by animals
having a nervous system in the course of evolution to
play a role in nervous system information transmission.
Adapted from Jiang et al., 2004.
Protein
subunit
Change in voltage
Voltage
sensor
(scorpion
venom)
Extracel lul ar fluid
Intr ace llu la r fluid
+
+ + +
Pore (tarantula toxin)
+
+
+
+
CH04.qxd 1/28/05 10:02 AM Page 127

water, which stops when the lever is released. This activity is
analogous to a graded potential.A harder lever press brings the
toilet to threshold and initiates flushing, a response that is out
of all proportion to the lever press. This activity is analogous to
the action potential.During the flush, the toilet is absolutely refractory,
meaning that another flush cannot be induced at this
time. During the refilling of the bowl, in contrast, the toilet is
relatively refractory, meaning that reflushing is possible but
harder to bring about.Only after the cycle is over and the toilet
is once again “resting,” can the usual flush be produced again.
The Nerve Impulse
Suppose you place two recording electrodes at a distance from
each other on an axon membrane and then electrically stimulate
an area adjacent to one of these electrodes. That electrode
would immediately record an action potential.A similar recording would register
on the second electrode in a flash. Apparently, an action potential has arisen near this
electrode also, even though this second electrode is some distance from the original
point of stimulation.
Is this second action potential simply an echo of the first that passes down the
axon? No, it cannot be, because the size and shape of the action potential are exactly
the same at the two electrodes. The second is not just a faint, degraded version of the
first but is equal in magnitude. Somehow the full action potential has moved along the
axon. This propagation of an action potential along an axon is called a nerve impulse.
Why does an action potential move? Remember that the total voltage change during
an action potential is 100 mV, far beyond the 20-mV change needed to bring the membrane
from its resting state of !70 mV to the threshold level of !50 mV. Consequently,
the voltage change on the part of the membrane at which an action potential first occurs
is large enough to bring adjacent parts of the membrane to a threshold of !50 mV.
When the membrane of an adjacent part of the axon reaches !50 mV, the voltagesensitive
channels at that location pop open to produce an action potential there as
well. This second occurrence, in turn, induces a change in the voltage of the membrane
still farther along the axon, and so on and on, down the axon’s length. Figure 4-15 illustrates
this process. The nerve impulse occurs because each action potential propagates
another action potential on an adjacent part of the axon membrane. The word
propagate means “to give birth,” and that is exactly what happens. Each successive action
potential gives birth to another down the length of the axon.
Two main factors ensure that a single nerve impulse of a constant size travels down
the axon:
1. Voltage-sensitive channels produce refractory periods. Although an action potential
can travel in either direction on an axon, refractory periods prevent it from reversing
direction and returning to the point from which came. Thus refractory
periods create a single, discrete impulse that travels only in one direction.
2. All action potentials generated as a nerve impulse travels are of the same magnitude.
An action potential depends on energy expended at the site where it occurs,
and the same amount of energy is expended at every site along the membrane
where a nerve impulse is propagated. As a result, there is no such thing as a dissipated
action potential. Simply stated, an action potential is either generated completely
or it is not generated at all, which means that a nerve impulse always
maintains a constant size.
128 ! CHAPTER 4
Nerve impulse. Propagation of an
action potential on the membrane of an
axon.
Node of Ranvier. The part of an axon
that is not covered by myelin.
Threshold
0
Depolarize Repolarize Resting Hyperpolarize Resting
Gate 1
(voltage sensitive)
Gate 2
(not voltage
sensitive) K+
K+ K+
Na+ K+ K+
Na+
Na+
Figure 4-14
Phases of an Action Potential
Initiated by changes in voltage-sensitive
sodium and potassium channels, an
action potential begins with a
depolarization (gate 1 of the sodium
channel opens and then gate 2 closes).
The slower-opening potassium-channel
gate contributes to repolarization and
hyperpolarization until the resting
membrane potential is restored.
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To summarize the action of a nerve impulse, think
of the voltage-sensitive channels along the axon as a series
of dominoes. When one domino falls, it knocks
over its neighbor, and so on down the line. The “wave”
cannot return the way that it has come.There is also no
decrement in the size of the fall. The last domino travels
exactly the same distance and falls just as hard as the
first one did.
Essentially this “domino effect” happens when
voltage-sensitive channels open. The opening of one channel produces a voltage
change that triggers its neighbor to open, just as one domino knocks over
the next.When gate 2 on a voltage-sensitive sodium channel closes, that channel
is inactivated,much as a domino is temporarily inactivated after it falls over.
Both channel and domino must be reset before they can work again. Finally, the
channel-opening response does not grow any weaker as it moves along the axon.
The last channel opens exactly like the first, just as the domino action stays constant
to the end of the line. Because of this behavior of voltage-sensitive channels,
a single nerve impulse of constant size moves in only one direction along
an axon.
Saltatory Conduction and Myelin Sheaths
Because the giant axons of squid are so large, they can transmit nerve impulses
very quickly, much as a large-diameter pipe can deliver a lot of water at a rapid
rate. But large axons take up substantial space, and so a squid cannot accommodate
many of them or its body would become too bulky. For us mammals,
with our many axons producing repertoires of complex behaviors, giant axons
are out of the question. Our axons must be extremely slender because our complex
behaviors require a great many of them.
Our largest axons are only about 30 lm wide; so the speed with which they convey
information should not be especially fast. And yet, like most vertebrate species,
we are hardly sluggish creatures. We process information and generate responses
with impressive speed. How do we manage to do so if our axons are so thin? The
vertebrate nervous system has evolved a solution that has nothing to do with axon
size.
Glial cells play a role in speeding nerve impulses in the vertebrate nervous system.
Schwann cells in the human peripheral nervous system and oligodendroglia in the central
nervous system wrap around each axon, insulating it except for a small, exposed gap
between each glial cell (Figure 4-16). As described in Chapter 3, this insulation is referred
to as myelin or as a myelin sheath, and insulated axons are said to be myelinated.
Action potentials cannot occur where myelin is wrapped around an axon. For one
thing, the myelin creates an insulating barrier to the flow of ionic current.
For another, regions of an axon that lie under myelin have few
channels through which ions can flow, and, as you know, such channels
are essential to generating an action potential.
But axons are not totally encased in myelin. Unmyelinated gaps
on the axon between successive glial cells are richly endowed with
voltage-sensitive channels. These tiny gaps in the myelin sheath, the
nodes of Ranvier, are sufficiently close to one another that an action
potential occurring at one node can trigger the opening of voltagesensitive
gates at an adjacent node. In this way, a relatively slow action
potential jumps at the speed of light from node to node, as shown in
Axon Voltage spread
Stimulator
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Voltage spread
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Voltage
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K+
Na+
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Figure 4-15
Propagating an Action Potential
Voltage sufficient to open Na" and K"
channels spreads to adjacent sites of the
membrane, inducing voltage-sensitive
gates to open. Here, voltage changes are
shown on only one side of the membrane.
The domino effect
(A) (B)
Wrapped
Axons myelin Axon
Oligodendrocyte
Wrapped
myelin
Nodes
of Ranvier
Schwann
cell
Node
of Ranvier
Figure 4-16
Myelination An axon is myelinated by
(A) oligodendroglia in the CNS and (B)
Schwann cells in the PNS. Each glial cell is
separated by a gap, or node of Ranvier.
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Axon
Schwann cell
(forms myelin)
(A)
Axon
Node
of Ranvier
Current flow
K+
Na+
Current flow
Current flow
K+
Na+
K+
Na+
Myelin
Node
of Ranvier
(B)
–70
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130 ! CHAPTER 4
Figure 4-17. This flow of energy is called saltatory conduction (from the Latin verb
saltare, meaning “to dance”).
Jumping from node to node greatly speeds the rate at which an action potential
can travel along an axon. On larger,myelinated mammalian axons, nerve impulses can
travel at a rate as high as 120 meters per second, compared with only about 30 meters
per second on smaller, uninsulated axons. Think of how a “wave” of consecutively
standing spectators travels around a football stadium. As one person rises, the adjacent
person rises, producing the wave effect. This wave is like conduction along an unmyelinated
axon. Now think of how much faster the wave would complete its circuit
around the field if only spectators in the corners rose to produce it, which is analogous
to a nerve impulse that travels by jumping from one node of Ranvier to the next. The
quick reactions of which humans and other mammals are capable are due in part to
this saltatory conduction in their nervous systems.
In Review .
Microelectrodes connected to a voltmeter and placed on either side of an axon membrane
will record a voltage difference across the membrane due to the unequal distribution of
ions inside and outside the cell. The semipermeable membrane prevents the efflux of large
protein anions, and it pumps sodium ions out of the cell. Although potassium ions and chloride
ions are relatively free to cross the membrane through their respective channels, the
equilibrium at which their concentration gradient matches their voltage gradient contributes
to the relative transmembrane difference of !70 mV in charge. Some sodium and
potassium channels sensitive to the membrane’s voltage open when the membrane is electrically
stimulated, allowing a brief free flow of ions across the membrane and stimulating
an action potential, a brief reversal of charge on the membrane. The voltage change
Saltatory conduction. Propagation of
an action potential at successive nodes of
Ranvier; saltatory means “jumping” or
“dancing.”
Figure 4-17
Saltatory Conduction
(A) Unmyelinated nodes of
Ranvier are rich in voltagesensitive
channels. (B) In
saltatory conduction, the
action potential jumps
from node to node.
On the Foundations CD, visit the
module on neural communications. In the
section on conduction of the action
potential you can watch an animation
showing the role of the myelin sheath in
conduction. Note the role of the nodes of
Ranvier in this process.