Membrane Potentials and Action potentials pdf - Membrane Physiology and Nerve and Muscle

changing diffusion potentials.

tions, create a membrane potential. In later sections of this chapter, we show

ions across a selectively permeable membrane can, under appropriate condi-

Thus, in both parts of Figure 5–1, we see that a concentration difference of

the fiber.

in the mammalian nerve fiber,

to block further net diffusion of sodium ions to the inside; however, this time,

ity inside. Again, the membrane potential rises high enough within milliseconds

, with negativity outside and positiv-

of opposite polarity to that in Figure 5–1

permeable to the sodium ions but impermeable to all other ions. Diffusion of

. These ions are also positively charged. This time, the membrane is highly

shows the same phenomenon as in Figure 5–1

Figure 5–1

with negativity inside the fiber membrane.

the potential difference required is about 94 millivolts,

mammalian nerve fiber,

exterior, despite the high potassium ion concentration gradient. In the normal

so, the potential difference between the inside and outside, called the

behind and do not diffuse outward with the potassium. Within a millisecond or

electrical charges to the outside, thus creating electropositivity outside the

to diffuse outward through the membrane. As they do so, they carry positive

toward outside, there is a strong tendency for extra numbers of potassium ions

other ions. Because of the large potassium concentration gradient from inside

the membrane. Let us assume that the

In Figure 5–1

“Diffusion Potential” Caused by an Ion Concentration Difference on the Two Sides of the

Membrane Potentials Caused by Diffusion

during action by nerve and muscle cells.

in membrane potentials also activate many of the cells’ functions. The present

cells, macrophages, and ciliated cells, local changes

branes. In still other types of cells, such as glandular

at their membranes, and these impulses are used to

such as nerve and muscle cells, are capable of gen-

virtually all cells of the body. In addition, some cells,

Action Potentials

Membrane Potentials and

Electrical potentials exist across the membranes of

erating rapidly changing electrochemical impulses

transmit signals along the nerve or muscle mem-

discussion is concerned with membrane potentials generated both at rest and

Basic Physics of Membrane Potentials

Membrane.

A, the potassium concentration is great inside a nerve

fiber membrane but very low outside
membrane in this instance is permeable to the potassium ions but not to any

membrane and electronegativity inside because of negative anions that remain

diffusion

potential, becomes great enough to block further net potassium diffusion to the

A, but this time

with high concentration of sodium ions outside the membrane and low sodium
inside

the positively charged sodium ions to the inside creates a membrane potential

the potential is about 61 millivolts positive inside

that many of the rapid changes in membrane potentials observed during nerve
and muscle impulse transmission result from the occurrence of such rapidly

ions, the diffusion potential that develops depends on

When a membrane is permeable to several different

Several Different Ions

When the Membrane Is Permeable to

Calculation of the Diffusion Potential

inside the membrane.

10 times that on the outside, the log of 10 is 1, so that

is negative (–) if the ion is positive. Thus, when the con-

fusing from inside to outside is a negative ion, and it

potential is the potential inside the membrane. Also,

membrane remains at zero potential, and the Nernst

When using this formula, it is usually assumed that

where EMF is electromotive force.

additional net diffusion. The following equation, called

for the ion to diffuse in one direction, and therefore

brane. The greater this ratio, the greater the tendency

duced in Chapter 4. The magnitude of this Nernst

for that ion, a term that was intro-

The diffusion potential level

Membrane Physiology, Nerve, and Muscle

Unit II

Relation of the Diffusion Potential to the Concentration Differ-
ence—The Nernst Potential.

across a membrane that exactly opposes the net diffu-
sion of a particular ion through the membrane is called
the Nernst potential

potential is determined by the ratio of the concentra-
tions of that specific ion on the two sides of the mem-

the greater the Nernst potential required to prevent

the Nernst equation, can be used to calculate the
Nernst potential for any univalent ion at normal body
temperature of 98.6°F (37°C):

the potential in the extracellular fluid outside the

the sign of the potential is positive (

+) if the ion dif-

centration of positive potassium ions on the inside is

the Nernst potential calculates to be –61 millivolts

61 log

EMF millivolts

Concentration inside

Concentration outside

(

)

= ±

The method for measuring the membrane potential is

of this chapter.

nerves, which is the subject of most of the remainder

does not change greatly during this process. Therefore,

changes during transmission of a nerve impulse,

Fourth, as explained later, the permeability of the

leaving the nondiffusible positive ions on the outside.

tively charged chloride ions diffuse to the inside, while

is, a chloride ion gradient from the

occurs when there is a gradient for a negative ion. That

electronegativity on the inside. The opposite effect

fusible negative anions on the inside, thus creating

concentration is higher inside than outside. This carries

ativity inside the membrane. The reason for this is that

Third, a positive ion concentration gradient from

them alone.

equal to the Nernst potential for sodium. The same

sodium ions alone, and the resulting potential will be

and chloride ions, the membrane potential becomes

brane permeability for that particular ion.That is, if the

Second, the degree of importance of each of the ions

system. The concentration gradient of each of these

bers, as well as in the neuronal cells in the nervous

equation. First, sodium, potassium, and chloride ions

), are involved.

univalent negative ion, chloride (Cl

), and one

tive ions, sodium (Na

the membrane. Thus, the following formula, called the

to each ion, and (3) the concentrations (

of each ion, (2) the permeability of the membrane (

three factors: (1) the polarity of the electrical charge

C) of the

respective ions on the inside (i) and outside (o) of

Goldman equation, or the Goldman-Hodgkin-Katz
equation, gives the calculated membrane potential on
the inside of the membrane when two univalent posi-

) and potassium (K

–

Let us study the importance and the meaning of this

are the most important ions involved in the develop-
ment of membrane potentials in nerve and muscle
fi

ions across the membrane helps determine the voltage
of the membrane potential.

in determining the voltage is proportional to the mem-

membrane has zero permeability to both potassium

entirely dominated by the concentration gradient of

holds for each of the other two ions if the membrane
should become selectively permeable for either one of

inside the membrane to the outside causes electroneg-

excess positive ions diffuse to the outside when their

positive charges to the outside but leaves the nondif-

outside to the inside

causes negativity inside the cell because excess nega-

sodium and potassium channels undergoes rapid

whereas the permeability of the chloride channels

rapid changes in sodium and potassium permeability
are primarily responsible for signal transmission in

Measuring the Membrane
Potential

simple in theory but often difficult in practice because

61 log

= -

◊

EMF millivolts

(

)

(+ 61 mV)

+ –
+ –
+ –
+ –
+ –
+ –
+ –

+ –
+ –

– +
– +
– +
– +
– +
– +
– +
– +
– +
– +

Nerve fiber

(Anions)

–

(Anions)

–

(– 94 mV)

– +
– +
– +
– +
– +
– +
– +

– +
– +

+ –
+ –
+ –
+ –
+ –
+ –
+ –
+ –
+ –
+ –

Nerve fiber

(Anions)

–

(Anions)

–

DIFFUSION POTENTIALS

ions diffuse and positive when sodium ions diffuse because of

that the internal membrane potential is negative when potassium

the nerve fiber membrane is permeable only to sodium ions. Note

Establishment of a “diffusion potential” when

cell to outside through a membrane that is selectively permeable

membrane, caused by diffusion of potassium ions from inside the

Establishment of a “diffusion” potential across a nerve fiber

Figure 5–1

only to potassium. B,

opposite concentration gradients of these two ions.

negative potential inside the cell membrane.

cit of positive ions on the inside; this causes a

ions to the inside), leaving a

4. Further, note that this is an

Figure 5

ions to the inside, as illustrated on the left-hand side in

First, let

Active Transport of Sodium and Potassium Ions Through the

the level of this resting potential, but before doing so,

paragraphs, we explain all the factors that determine

ber. In the next few

millivolts. That is, the potential

The resting membrane potential of large nerve

of Nerves

quent sections of this chapter.

as 1/10,000 of a second. Rapid shifting of ions in this

ber needs to be transferred. Also, an

ber; this means that only

3. Therefore, an incredibly small

panel of Figure 5

can be both positive and negative, as shown in the upper

outward. All the remaining ions inside the nerve

To create a negative potential inside the membrane,

ber.

ber,

90 millivolts. Moving across the center of the

), the potential decreases abruptly

electrical dipole layer

Then, as the recording electrode passes through the

is zero, which is the potential of the extracellular

is outside the nerve membrane, the recorded potential

gure and passing to the right. As long as the electrode

ber membrane, beginning at the left side of the

The lower part of Figure 5

chapter.

connected to an oscilloscope, as explained later in the

transmission of nerve impulses, the microelectrode is

changes

and a resistance more than a million ohms. For record-

ow through the tip of the micropipette, which

ate voltmeter. This voltmeter is a highly sophisticated

uid, and the potential difference between the inside

indifferent electrode,

ber. Then another electrode, called

lled with an electrolyte solution. The

bers. Figure 5

Membrane Potentials and Action Potentials

Chapter 5

of the small size of most of the fi

–2 shows

a small pipette fi
pipette is impaled through the cell membrane to
the interior of the fi
the “

” is placed in the extracellular

fl
and outside of the fiber is measured using an appropri-

electronic apparatus that is capable of measuring very
small voltages despite extremely high resistance to elec-
trical fl
has a lumen diameter usually less than 1 micrometer

ing rapid

in the membrane potential during

–3 shows the electrical

potential that is measured at each point in or near the
nerve fi
fi

fluid.

voltage change area at the cell membrane (called the

to –

the potential remains at a steady –90-millivolt level but
reverses back to zero the instant it passes through the
membrane on the opposite side of the fi

only enough positive ions to develop the electrical
dipole layer at the membrane itself must be transported

fiber

–

number of ions needs to be transferred through the
membrane to establish the normal “resting potential” of
–90 millivolts inside the nerve fi
about 1/3,000,000 to 1/100,000,000 of the total positive
charges inside the fi

equally small number of positive ions moving from
outside to inside the fiber can reverse the potential from
–90 millivolts to as much as

+35 millivolts within as little

manner causes the nerve signals discussed in subse-

Resting Membrane Potential

fibers

when not transmitting nerve signals is about –90

inside the fiber is 90

millivolts more negative than the potential in the extra-
cellular fluid on the outside of the fi

we must describe the transport properties of the resting
nerve membrane for sodium and potassium.

Membrane—The Sodium-Potassium (Na

-K

) Pump.

us recall from Chapter 4 that all cell membranes of the
body have a powerful Na

-K

that continually pumps

sodium ions to the outside of the cell and potassium

–

electrogenic

pump because more positive charges are pumped to
the outside than to the inside (three Na

ions to the

outside for each two K

net defi

+ + + + + + + + +

+ + + + + + + +

+ + + + + + + + + + +

+ + + + +

—

Silver–silver

chloride

electrode

KCI

– – – – – – – – –

– – – – – – –

(– 90

mV)

– – – – – – – – – –

– – – – –

a microelectrode.

Measurement of the membrane potential of the nerve fiber using

Figure 5–2

–90

Electrical potential

(millivolts)

– + – + – + – + – + – + – + –
+ – + + – – + – + – – + + – +
– + – + – + – + – + – + – + –
+ – + + – – + – + – – + + – +
– + – + – + – + – + – + – + –
+ – + + – – + – + – – + + – +
– + – + – + – + – + – + – + –
+ – + + – – + – + – – + + – +
– + – + – + – + – + – + – + –
+ – + + – – + – + – – + + – +

Nerve fiber

the fiber.

surface. The lower panel displays the abrupt changes in mem-

surface of the membrane and positive charges along the outside

cellular fluid surrounding a nerve fiber and in the fluid inside the

Figure 5–3

Distribution of positively and negatively charged ions in the extra-

fiber; note the alignment of negative charges along the inside

brane potential that occur at the membranes on the two sides of

of the nerve membrane to sodium ions, caused by the

Figure 5

Contribution of Sodium Diffusion Through the Nerve Membrane.

gure.

millivolts, as shown in the

would be equal to

were the only factor causing the resting potential, the

94 millivolts. Therefore, if potassium ions

because the logarithm of 35 is 1.54, and this times

potassium ions inside to outside, 35:1, the Nernst

outside the membrane. Because of the high ratio of

potassium ions, as demonstrated by the open channels

In Figure

90 millivolts. They are as follows.

Figure 5

Origin of the Normal Resting

later, this differential in permeability is exceedingly

normally about 100 times as permeable. As discussed

potassium leakage because, on average, the channels

The emphasis is on

channel.

sium and sodium ions can leak, called a

The right side of Figure 5

Leakage of Potassium and Sodium Through the Nerve Mem-

The ratios of these two respective ions from the inside

(inside):

140 mEq/L

(outside):

4 mEq/L

(inside):

14 mEq/L

(outside):

142 mEq/L

membrane. These gradients are the following:

The Na

Membrane Physiology, Nerve, and Muscle

Unit II

-K

also causes large concentration gradi-

ents for sodium and potassium across the resting nerve

to the outside are

inside

/Na

outside

= 0.1

inside

outside

= 35.0

brane.

–4 shows a channel

protein in the nerve membrane through which potas-

potassium-

sodium (K

-Na

) “leak”

are far more permeable to potassium than to sodium,

important in determining the level of the normal
resting membrane potential.

Membrane Potential

–5 shows the important factors in the estab-

lishment of the normal resting membrane potential of
–

Contribution of the Potassium Diffusion Potential.

5–5A, we make the assumption that the only move-
ment of ions through the membrane is diffusion of

between the potassium symbols (K

) inside and

potential corresponding to this ratio is –94 millivolts

–61

millivolts is –

resting potential inside the fiber

–94

–5B shows the addition of slight permeability

minute diffusion of sodium ions through the K

-Na

ATP

3Na

-K

pump

-Na

"leak" channels

ADP

Outside

“leak” channels. ADP, adenosine diphosphate; ATP, adenosine

Figure 5–4

Functional characteristics of the Na

-K

pump and of the K

-Na

triphosphate.

Diffusion

4 mEq/L

140 mEq/L

142 mEq/L

4 mEq/L

142 mEq/L

14 mEq/L

+
+

+
+
+
+

-
-

-
-
-
-

+
+
+
+
+
+

-
-
-
-
-
-

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

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

(Anions)

(–90 mV)

4 mEq/L

pump

140 mEq/L

(

94 mV)

(–94 mV)

14 mEq/L

(

61 mV)

(–86 mV)

140 mEq/L

(–94 mV)

when the membrane potential is caused by diffusion

potential is caused by diffusion of both sodium and potassium

entirely by potassium diffusion alone;

under three conditions:

Establishment of resting membrane potentials in nerve fibers

Figure 5–5

A, when the membrane potential is caused

B, when the membrane

ions; and C,
of both sodium and potassium ions plus pumping of both these
ions by the Na

-K

pump.

bers, as well as in

somewhat positive. In some smaller

bers, the great excess of positive sodium ions moving

In large nerve

direction. This is called

ions, with the potential rising rapidly in the positive

ions to diffuse to the interior of the axon. The normal

denly becomes very permeable to sodium ions, allow-

At this time, the membrane sud-

before the action potential begins. The membrane is

This is the resting membrane potential

follows.

The successive stages of the action potential are as

almost equally rapid recovery.

over a few 10,000ths of a second, illustrating the

the exterior at its end. The lower panel shows graphi-

tial, with transfer of positive charges to the interior of

The upper panel of Figure 5

To conduct a nerve signal, the action potential moves

ber membrane.

action potentials,

Nerve Action Potential

90 millivolts.

pump, giving a net membrane potential

this being determined by potassium diffusion. Then, an

86 millivolts, almost all of

In summary, the diffusion potentials alone caused by

90 millivolts.

diffusion alone. Therefore, as shown in Figure 5

from inside the membrane; this creates an additional

inside of the membrane. The fact that more sodium

gure, there

tribution to the resting potential. In this

, the

In Figure 5

gure.

86 millivolts, which is near

100 times as great as its permeability to sodium. Using

ber, the

the diffusion of sodium. In the normal nerve

sodium, it is logical that the diffusion of potassium con-

Intuitively, one can see that if the membrane is highly

by using the Goldman equation described previously.

will be the summated potential? This can be answered

volts. How do these interact with each other, and what

61 millivolts. But also shown in Figure 5

outside the membrane is 0.1, and this gives a calculated

leak channels. The ratio of sodium ions from inside to

Membrane Potentials and Action Potentials

Chapter 5

Nernst potential for the inside of the membrane of
+

–5B is the

Nernst potential for potassium diffusion of –94 milli-

permeable to potassium but only slightly permeable to

tributes far more to the membrane potential than does

permeability of the membrane to potassium is about

this value in the Goldman equation gives a potential
inside the membrane of –
the potassium potential shown in the fi

Contribution of the Na

-K

Pump.

–5C

-K

pump is shown to provide an additional con-

is continuous pumping of three sodium ions to the
outside for each two potassium ions pumped to the

ions are being pumped to the outside than potassium
to the inside causes continual loss of positive charges

degree of negativity (about –4 millivolts additional) on
the inside beyond that which can be accounted for by

–5C,

the net membrane potential with all these factors
operative at the same time is about –

potassium and sodium diffusion would give a mem-
brane potential of about –

additional –4 millivolts is contributed to the mem-
brane potential by the continuously acting electro-
genic Na

-K

of –

Nerve signals are transmitted by
which are rapid changes in the membrane potential
that spread rapidly along the nerve fi
Each action potential begins with a sudden change
from the normal resting negative membrane potential
to a positive potential and then ends with an almost
equally rapid change back to the negative potential.

along the nerve fiber until it comes to the fiber’s
end.

–6 shows the changes

that occur at the membrane during the action poten-

the fiber at its onset and return of positive charges to

cally the successive changes in membrane potential

explosive onset of the action potential and the

Resting Stage.

said to be “polarized” during this stage because of the
–90 millivolts negative membrane potential that is
present.

Depolarization Stage.

ing tremendous numbers of positively charged sodium

“polarized” state of –90 millivolts is immediately neu-
tralized by the inflowing positively charged sodium

depolarization.

fi
to the inside causes the membrane potential to actu-
ally “overshoot” beyond the zero level and to become

KCI

+ + + +

+ + + + + +

0.1 0.2 0.3 0.4 0.5 0.6 0.7

+35

–90

Millivolts

Overshoot

Milliseconds

riz

tio

Resting

—

+ + + + +

Silver–silver

chloride

electrode

+ + + + – – – – – –

– – – –

+ + + +

– – – – –

– – – –

upper panel of the figure.

Typical action potential recorded by the method shown in the

Figure 5–6

opening of the potassium channels, for the most part,

channel. However, because of the slight delay in

90 millivolts toward zero, this voltage change causes

exterior. When the membrane potential rises from

sium channel is closed, and potassium ions are pre-

(right). During the resting state, the gate of the potas-

potassium channel in two states: during the resting

The lower panel of Figure 5

Voltage-Gated Potassium Channel and

rst repolarizing.

potential level. Therefore, it usually is not possible for

membrane state, which is the repolarization process.

inside of the membrane. At this point, the membrane

gate closes, and sodium ions no longer can pour to the

open for a few 10,000ths of a second, the inactivation

Therefore, after the sodium channel has remained

formational change that opens the activation gate.

a second after the activation gate opens. That is, the

inactivation gate, however, closes a few 10,000ths of

activation gate also closes the inactivation gate. The

channel. The same increase in voltage that opens the

of Figure 5

The upper right panel

inward through the channel, increasing the sodium

during this state, sodium ions can pour

the way to the open position. This is called the

mational change in the activation gate,

90 millivolts toward zero, it

resting state, rising from

When the membrane

ber through these sodium channels.

90 millivolts. In this state, the activation gate is closed,

The upper left of the

inactivation gate.

activation gate,

sodium channel in three separate states. This channel

The upper panel of Figure 5

Voltage-Gated Sodium Channel—Activation

channels.

These two voltage-gated channels are

the membrane.

voltage-gated potassium channel

voltage-gated sodium channel.

The necessary actor in causing both depolarization

Potassium Channels

Voltage-Gated Sodium and

voltage-gated sodium and potassium channels.

port channels through the nerve membrane: the

depolarization and repolarization, we need to describe

To explain more fully the factors that cause both

membrane.

brane potential. This is called

Then, rapid diffusion of potassium ions to the exterior

sodium ions, the sodium channels begin to close and

Within a few 10,000ths of a second

shoot to the positive state.

many central nervous system neurons, the potential

Membrane Physiology, Nerve, and Muscle

Unit II

merely approaches the zero level and does not over-

Repolarization Stage.

after the membrane becomes highly permeable to

the potassium channels open more than normal.

re-establishes the normal negative resting mem-

repolarization of the

the special characteristics of two other types of trans-

and repolarization of the nerve membrane during the
action potential is the

also plays an impor-

tant role in increasing the rapidity of repolarization of

in addition to the Na

-K

pump and the K

-Na

leak

and Inactivation of the Channel

–7 shows the voltage-gated

has two gates—one near the outside of the channel
called the

and another near the inside

called the

figure

depicts the state of these two gates in the normal
resting membrane when the membrane potential is
–
which prevents any entry of sodium ions to the inte-
rior of the fi

Activation of the Sodium Channel.

potential becomes less negative than during the

–

finally reaches a voltage—usually somewhere between
–70 and –50 millivolts—that causes a sudden confor-

flipping it all

acti-

vated state;

permeability of the membrane as much as 500- to
5000-fold.

Inactivation of the Sodium Channel.

–7 shows a third state of the sodium

conformational change that flips the inactivation gate
to the closed state is a slower process than the con-

potential begins to recover back toward the resting

Another important characteristic of the sodium

channel inactivation process is that the inactivation
gate will not reopen until the membrane potential
returns to or near the original resting membrane

the sodium channels to open again without the nerve
fiber’s fi

Its Activation

–7 shows the voltage-gated

state (left) and toward the end of the action potential

vented from passing through this channel to the

–
a conformational opening of the gate and allows
increased potassium diffusion outward through the

90 mV,

Activation

gate

Inactivation

gate

Inside

Resting

(

90 mV)

Activated

(

90 to

35 mV)

Inactivated

(

35 to

delayed)

Resting

(

90 mV)

Slow activation

(

35 to

90 mV)

normal resting negative value to a positive value.

sium channels when the membrane potential is changed from the

Figure 5–7

Characteristics of the voltage-gated sodium (top) and potassium
(bottom) channels, showing successive activation and inactiva-
tion of the sodium channels and delayed activation of the potas-

value.

closed. Further, once the potassium channels open, they

nels. These open slowly and reach their full open state

tive value. However, during the next millisecond or so,

90 millivolts.

and then, 2 milliseconds later, back to

Figure 5

ber.

activation gates are located. Conversely,

tetrodotoxin

channel at a time. For instance, the sodium channels can

potassium is the only permeant ion, current

ow only through the sodium channels. When

and outside the squid axon, the voltage clamp measures

some cases is as large as 1 millimeter in diameter. When

crustaceans, especially the giant squid axon, which in

easily when using large nerve

ber and repeats the study. This can be done

8. Finally, the

the screen of the oscilloscope in Figure 5

ow, as demonstrated on

instant, the current electrode is connected to an oscillo-

ow through the membrane channels. To

steady zero level. To achieve this, the current injected

cellular voltage, electrical current is injected automati-

through the channels. To counterbalance the effect of

open, and sodium and potassium ions begin to pour

zero, the voltage-gated sodium and potassium channels

the operator. When the membrane potential is suddenly

as measured by the voltage electrode, at the level set by

trode at whatever rate is required to hold the voltage,

the desired voltage, and this automatically injects either

ber. The

following way: The investigator decides which voltage

ber. This apparatus is used in the

tial, and the other is to conduct electrical current into

ber. One of

through the different channels. In using this apparatus,

voltage clamp,

Figure 5

these studies is shown in Figures 5

entists responsible, Hodgkin and Huxley. The essence of

The original research that led to quantitative

and Closing of the Voltage-Gated Channels—The “Voltage

Research Method for Measuring the Effect of Voltage on Opening

combine to speed the repolarization process, leading

Thus, the decrease in sodium entry to the cell and the

Membrane Potentials and Action Potentials

Chapter 5

they open just at the same time that the sodium chan-
nels are beginning to close because of inactivation.

simultaneous increase in potassium exit from the cell

to full recovery of the resting membrane potential
within another few 10,000ths of a second.

Clamp.”

understanding of the sodium and potassium channels
was so ingenious that it led to Nobel Prizes for the sci-

–8 and 5–9.

–8 shows an experimental apparatus called a

which is used to measure flow of ions

two electrodes are inserted into the nerve fi
these is to measure the voltage of the membrane poten-

or out of the nerve fi

he or she wants to establish inside the nerve fi
electronic portion of the apparatus is then adjusted to

positive or negative electricity through the current elec-

increased by this voltage clamp from –90 millivolts to

these ion movements on the desired setting of the intra-

cally through the current electrode of the voltage clamp
to maintain the intracellular voltage at the required

must be equal to but of opposite polarity to the net
current fl
measure how much current flow is occurring at each

scope that records the current fl

–

investigator adjusts the concentrations of the ions to
other than normal levels both inside and outside the
nerve fi

fibers removed from some

sodium is the only permeant ion in the solutions inside

current fl

flow only

through the potassium channels is measured.

Another means for studying the flow of ions through

an individual type of channel is to block one type of

be blocked by a toxin called

by applying it

to the outside of the cell membrane where the sodium

tetraethylam-

monium ion blocks the potassium channels when it is
applied to the interior of the nerve fi

–9 shows typical changes in conductance of

the voltage-gated sodium and potassium channels when
the membrane potential is suddenly changed by use of
the voltage clamp from –90 millivolts to

+10 millivolts

–

Note the sudden opening of the sodium channels (the
activation stage) within a small fraction of a millisecond
after the membrane potential is increased to the posi-

the sodium channels automatically close (the inactiva-
tion stage).

Note the opening (activation) of the potassium chan-

only after the sodium channels have almost completely

remain open for the entire duration of the positive
membrane potential and do not close again until after
the membrane potential is decreased back to a negative

Current

electrode

Voltage

electrode

Amplifier

Electrode

in fluid

“Voltage clamp” method for studying flow of ions through specific

Figure 5–8

channels.

90 mV

+10 mV

(mmho

/cm

Conductance

)

Time (milliseconds)

–

– 90 mV

Membrane potential

Activation

tiva

channel

before the end of the 2 milliseconds, whereas the potassium chan-

10 millivolts for 2 milliseconds. This figure shows that the

from the normal resting value of –90 millivolts to a positive value

channels when the membrane potential is suddenly increased

Typical changes in conductance of sodium and potassium ion

Figure 5–9

sodium channels open (activate) and then close (inactivate)

nels only open (activate), and the rate of opening is much slower
than that of the sodium channels.

smooth muscle, the fast sodium channels are hardly

muscle and smooth muscle. In fact, in some types of

fast channels.

in contrast to the sodium channels, which are called

nels,

slow chan-

sodium channels. Therefore, they are called

The calcium channels are slow to become activated,

channels.

fore, these channels are also called

ber. There-

well as to calcium ions; when they open, both calcium

These channels are slightly permeable to sodium ions as

In addition, there are voltage-gated calcium channels.

molar.

molar, in contrast to an external con-

This leaves an internal cell concentration of calcium

the sodium pump, the calcium pump pumps calcium

some cells to cause most of the action potential. Like

body have a calcium pump similar to the sodium pump,

The membranes of almost all cells of the

sium ions and other positive ions.

anions. Therefore, these impermeant negative ions are

the axon, any de

so forth. Because these ions cannot leave the interior of

organic phosphate compounds, sulfate compounds, and

that cannot go through the membrane channels. They

Impermeant Negatively Charged Ions (Anions) Inside the Nerve

sidered: negative anions and calcium ions.

potential. At least two other types of ions must be con-

Thus far, we have considered only the roles of sodium

sodium ions to the interior. Consequently, the action

conductance. This allows very rapid loss of potassium

open, so that the ratio of conductance shifts far in

positive at the action potential onset. Then the sodium

ber than do potassium ions to the exterior. This

Therefore, far more sodium ions

of the action potential, the ratio of sodium to potas-

is the action potential itself. During the early portion

each instant during the action potential, and above this

The middle portion of Figure 5

an additional millisecond or more delay.

close back to their original status, but again, only after

action potential, the return of the membrane potential

ond after the sodium channels open. At the end of the

voltage gating of the potassium channels, causing them

ond. The onset of the action potential also causes

ductance. Then the inactivation process closes the

However, at the onset of the action potential, the

sium ions than sodium ions through the leak channels.

ions. This is caused by much greater leakage of potas-

potential begins, the conductance for potassium ions is

ions. During the resting state, before the action

potential. The bottom of the

Figure 5

the Action Potential

Membrane Physiology, Nerve, and Muscle

Unit II

Summary of the Events That Cause

–10 shows in summary form the sequential

events that occur during and shortly after the action

figure shows the changes

in membrane conductance for sodium and potassium

50 to 100 times as great as the conductance for sodium

sodium channels instantaneously become activated
and allow up to a 5000-fold increase in sodium con-

sodium channels within another fraction of a millisec-

to begin opening more slowly a fraction of a millisec-

to the negative state causes the potassium channels to

–10 shows the ratio

of sodium conductance to potassium conductance at

sium conductance increases more than 1000-fold.

flow to the interior of

the fi
is what causes the membrane potential to become

channels begin to close and the potassium channels to

favor of high potassium conductance but low sodium

ions to the exterior but virtually zero flow of

potential quickly returns to its baseline level.

Roles of Other Ions During
the Action Potential

and potassium ions in the generation of the action

Axon.

Inside the axon are many negatively charged ions

include the anions of protein molecules and of many

ficit of positive ions inside the mem-

brane leaves an excess of these impermeant negative

responsible for the negative charge inside the fiber
when there is a net deficit of positively charged potas-

Calcium Ions.

and calcium serves along with (or instead of) sodium in

ions from the interior to the exterior of the cell mem-
brane (or into the endoplasmic reticulum of the cell),
creating a calcium ion gradient of about 10,000-fold.

ions of about 10

–7

centration of about 10

–3

and sodium ions flow to the interior of the fi

-Na

requiring 10 to 20 times as long for activation as the

Calcium channels are numerous in both cardiac

+ 20

+ 40

+ 60

1.5

(mmho

/cm

Conductance

)

conductance

Milliseconds

0.5

1.0

0.1

0.01

0.005

100

0.001

0.01

0.1

100

Overshoot

Positive

afterpotential

– 20
– 40
– 60
– 80
–100

Membrane potential (mV)

Action potential
Ratio of conductances
Na

sented in papers by Hodgkin and Huxley but transposed from

period thereafter. (These curves were constructed from theory pre-

during the latter stages of the action potential and for a short

tial, whereas potassium conductance increases only about 30-fold

course of the action potential. Sodium conductance increases

Figure 5–10

Changes in sodium and potassium conductance during the

several thousand-fold during the early stages of the action poten-

squid axon to apply to the membrane potentials of large mam-
malian nerve fibers.)

These positive charges increase the voltage for a dis-

brane areas. That is, positive electrical charges are

increased permeability to sodium. The arrows show a

that is, the midportion suddenly develops

ber, and Figure 5

11. Figure 5

nism is demonstrated in Figure 5

the action potential along the membrane. This mecha-

portions of the membrane, resulting in propagation of

However, an action potential elicited at any one point

potential as it occurs at one spot on the membrane.

In the preceding paragraphs, we discussed the action

Propagation of the

potential. This level of

to 30 millivolts usually is required. Therefore, a sudden

ber. A sudden rise in membrane potential of 15

cycle described in the preceding paragraph. This

tial soon terminates.

opening of potassium channels, and the action poten-

tion of a millisecond, the rising membrane potential

become activated (opened). Then, within another frac-

cycle that, once the feedback is strong enough, contin-

ber. This process is a positive-feedback vicious

causes a further rise in the membrane potential, thus

ow of sodium ions, which

opening. This allows rapid in

volts toward the zero level, the rising voltage itself

normal nerve. However, if any event causes enough

remains undisturbed, no action potential occurs in the

First, as long as the membrane of the nerve

action potential. The answer is quite simple.

itself, but we have not explained what initiates the

sodium and potassium permeability of the membrane,

Up to this point, we have explained the changing

Initiation of the Action Potential

open the sodium gate.

itself, in this way altering the voltage level required to

molecule. The positive charges of these calcium ions

sodium channels is as follows: These ions appear to bind

The probable way in which calcium ions affect the

respiratory muscles.

This is

tetany.

peripheral nerves, often causing muscle

remaining in the resting state. In fact, the calcium ion

ber becomes highly excitable, sometimes dis-

tial from its normal, very negative level. Therefore, the

calcium ions, the sodium channels become activated

channels become activated. When there is a de

The concentration of

entirely by activation of slow calcium channels.

present, so that the action potentials are caused almost

Membrane Potentials and Action Potentials

Chapter 5

Increased Permeability of the Sodium Channels When
There Is a Deficit of Calcium Ions.

calcium ions in the extracellular fluid also has a pro-
found effect on the voltage level at which the sodium

ficit of

(opened) by very little increase of the membrane poten-

nerve fi
charging repetitively without provocation rather than

concentration needs to fall only 50 per cent below
normal before spontaneous discharge occurs in some

“

”

sometimes lethal because of tetanic contraction of the

to the exterior surfaces of the sodium channel protein

in turn alter the electrical state of the channel protein

as well as the development of the action potential

A Positive-Feedback Vicious Cycle Opens the Sodium Channels.

fiber

initial rise in the membrane potential from –90 milli-

causes many voltage-gated sodium channels to begin

opening still more voltage-gated sodium channels and
allowing more streaming of sodium ions to the interior
of the fi

ues until all the voltage-gated sodium channels have

causes closure of the sodium channels as well as

Threshold for Initiation of the Action Potential.

An action

potential will not occur until the initial rise in mem-
brane potential is great enough to create the vicious

occurs when the number of Na

ions entering the fiber

becomes greater than the number of K

ions leaving

the fi

increase in the membrane potential in a large nerve

fiber from –90 millivolts up to about –65 millivolts
usually causes the explosive development of an action

–65 millivolts is said to be the

threshold for stimulation.

Action Potential

on an excitable membrane usually excites adjacent

–

–11A

shows a normal resting nerve fi

–11B

shows a nerve fiber that has been excited in its mid-
portion—

“local circuit” of current flow from the depolarized
areas of the membrane to the adjacent resting mem-

carried by the inward-diffusing sodium ions through
the depolarized membrane and then for several mil-
limeters in both directions along the core of the axon.

tance of 1 to 3 millimeters inside the large myelinated

+ + + +

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

+ +

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

+ + + + + + + + +

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

+ + + + + + + + +

+ + + + + + + + + + + + – –

– –

+ + + + + + + + + + – – – – + + + + + + + +

– –

+ + – – – – – – – – – – – – – – – – – – + +

+ + – – – – – – – – – – – – – – – – – –

– – – – – – – – – – – – + + – – – – – – – – –

– – – – – – – – – – – – – – – – – – – – – – –

– – – – – – – – – – – – + + – – – – – – – – –

– – – – – – – – – – + + + + – – – – – – – –

– – – – – – – – – –

– – – – – – – –

ductive fiber.

Propagation of action potentials in both directions along a con-

Figure 5–11

factors. First, in heart muscle, two types of channels

The cause of the plateau is a combination of several

bers,

greatly prolongs the period of depolarization. This

13; one can readily see that the plateau

in Figure 5

does repolarization begin. Such a plateau is shown

spike potential for many milliseconds, and only then

repolarize immediately after depolarization; instead,

In some instances, the excited membrane does not

ber can be

about eightfold. Therefore, it is easy to understand

concentration rises from 10 to 20 mEq/L, the activity

sodium concentration. That is, as the internal sodium

fact, the pumping activity increases approximately in

sodium ions accumulate inside the cell membrane. In

ATPase pump is that

when the nerve impulse frequency increases.

recharging, which is a measure of energy expenditure

12 shows

(ATP) energy system of the cell. Figure 5

ber is an active metabolic process, using

pump requires energy for operation, this

pump. Because this

is, sodium ions that have diffused to the interior of the

the original establishment of the resting potential.That

This is achieved by action of the Na

and potassium membrane concentration differences.

time, it becomes necessary to re-establish the sodium

that action potential conduction ceases. Even so, with

it cannot be measured. Indeed, 100,000 to 50 million

single action potential, this effect is so minute that

diffuse to the outside during repolarization. For a

outside the membrane, because sodium ions diffuse to

The transmission of each action potential along a

of Energy Metabolism

Completed—Importance

After Action Potentials Are

greater than 1

greater than 1. This

gation of an impulse to occur, the ratio of action poten-

depolarization stops. Therefore, for continued propa-

of the membrane. When this occurs, the spread of

excitable tissues. Occasionally, the action potential

all-or-nothing principle,

not travel at all if conditions are not right. This is called

the entire membrane if conditions are right, or it does

ber, the depolarization process travels over

All-or-Nothing Principle.

of propagation, but the action potential travels in all

11, an excitable membrane has no single direction

As demonstrated in Figure

muscle impulse.

ber. This trans-

depolarization. Thus, the depolarization process

the membrane, causing progressively more and more

tial spreads. These newly depolarized areas produce

Figure 5

in these new areas immediately open, as shown in

ing an action potential. Therefore, the sodium channels

Membrane Physiology, Nerve, and Muscle

Unit II

fiber to above the threshold voltage value for initiat-

–11C and D, and the explosive action poten-

still more local circuits of current flow farther along

travels along the entire length of the fi
mission of the depolarization process along a nerve or
muscle fiber is called a nerve or

Direction of Propagation.

5–

directions away from the stimulus—even along all
branches of a nerve fiber—until the entire membrane
has become depolarized.

Once an action potential has

been elicited at any point on the membrane of a
normal fi

the

and it applies to all normal

reaches a point on the membrane at which it does not
generate sufficient voltage to stimulate the next area

tial to threshold for excitation must at all times be

“

” requirement is

called the safety factor for propagation.

Re-establishing Sodium and
Potassium Ionic Gradients

nerve fiber reduces very slightly the concentration
differences of sodium and potassium inside and

the inside during depolarization and potassium ions

impulses can be transmitted by large nerve fibers
before the concentration differences reach the point

-K

pump in the

same way as described previously in the chapter for

cell during the action potentials and potassium ions
that have diffused to the exterior must be returned to

their original state by the Na

-K

“recharging”

of the nerve fi
energy derived from the adenosine triphosphate

–

that the nerve fiber produces excess heat during

A special feature of the Na

-K

its degree of activity is strongly stimulated when excess

proportion to the third power of this intracellular

of the pump does not merely double but increases

how the “recharging” process of the nerve fi
set rapidly into motion whenever the concentration
differences of sodium and potassium ions across the
membrane begin to “run down.”

Plateau in Some Action
Potentials

the potential remains on a plateau near the peak of the

–

type of action potential occurs in heart muscle fi
where the plateau lasts for as long as 0.2 to 0.3 second
and causes contraction of heart muscle to last for this
same long period.

100

200

300

Heat production

Impulses per second

At rest

increasing rates of stimulation.

Heat production in a nerve fiber at rest and at progressively

Figure 5–12

becomes excessively permeable to potassium ions. The

tinuing for a short period thereafter, the membrane

that toward the end of each action potential, and con-

14. This shows

in Figure 5

before the onset of the next action potential? The

polarized, rather than delaying for nearly a second

Why does the membrane of the heart control center

tissue.

neously. This cycle continues over and over and causes

tion again, and a new action potential occurs sponta-

seconds, spontaneous excitability causes depolariza-

polarizes. After another delay of milliseconds or

at the end of the action potential, the membrane re-

and so on, until an action potential is generated. Then,

ow inward; and (4) the permeability increases more,

increases membrane permeability; (3) still more ions

brane voltage in the positive direction, which further

ow inward; (2) this increases the mem-

the following sequence occurs: (1) some sodium and

sodium and calcium channels totally closed. Therefore,

volts. This is not enough negative voltage to keep the

14 shows

membrane depolarization. Thus, Figure 5

For spontaneous rhythmicity to occur, the membrane

Re-excitation Process Necessary for Spontaneous Rhythmicity.

permeability of the membrane.

below a critical value, both of which increase sodium

normally are highly stable, discharge repetitively when

bers, which

tissue cells is reduced low enough. For instance, even

Also, almost all other excitable tissues can discharge

breathing.

heart, (2) rhythmical peristalsis of the intestines, and

neurons of the central nervous system. These rhyth-

the heart, in most smooth muscle, and in many of the

EXCITABLE TISSUES—

90 millivolts.

very much until the end of the plateau. This delays the

nels are slower than usual to open, often not opening

ber,

spike portion of the action potential, whereas the slow,

slow channels.

nels, which are slow to open and therefore are called

nels,

fast chan-

voltage-activated sodium channels, called

enter into the depolarization process: (1) the usual

Membrane Potentials and Action Potentials

Chapter 5

and (2) voltage-activated calcium-sodium chan-

Opening of fast channels causes the

prolonged opening of the slow calcium-sodium chan-
nels mainly allows calcium ions to enter the fi
which is largely responsible for the plateau portion of
the action potential as well.

A second factor that may be partly responsible for

the plateau is that the voltage-gated potassium chan-

return of the membrane potential toward its normal
negative value of –80 to –

RHYTHMICITY OF SOME

REPETITIVE DISCHARGE

Repetitive self-induced discharges occur normally in

mical discharges cause (1) the rhythmical beat of the

(3) such neuronal events as the rhythmical control of

repetitively if the threshold for stimulation of the

large nerve fibers and skeletal muscle fi

they are placed in a solution that contains the drug
veratrine or when the calcium ion concentration falls

even in its natural state must be permeable enough to
sodium ions (or to calcium and sodium ions through
the slow calcium-sodium channels) to allow automatic

–

that the “resting” membrane potential in the rhythmi-
cal control center of the heart is only –60 to –70 milli-

calcium ions fl

self-induced rhythmical excitation of the excitable

not depolarize immediately after it has become re-

answer can be found by observing the curve labeled
“potassium conductance”

–

excessive outflow of potassium ions carries tremen-
dous numbers of positive charges to the outside of the

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

+60

+40

+20

–20

–40

–60

–80

–100

Millivolts

Plateau

Seconds

Action potential (in millivolts) from a Purkinje fiber of the heart,

Figure 5–13

showing a “plateau.”

Seconds

+60

+40

+20

– 20

– 40

– 60

Millivolts

Potassium

conductance

Hyperpolarization

Rhythmical

action

potentials Threshold

in the rhythmical control center of the heart. Note their relationship

Rhythmical action potentials (in millivolts) similar to those recorded

Figure 5–14

to potassium conductance and to the state of hyperpolarization.

node, exciting successive nodes one after another. Thus,

That is,

17; this is called

Figure 5

tials are conducted from node to node, as shown in

Yet the action poten-

only at the nodes.

ease through the nodes of Ranvier. Therefore, action

myelin sheaths of myelinated nerves, they can

“Saltatory” Conduction in Myelinated Fibers from Node to Node.

node of Ranvier.

axon. This area is called the

along the axon, a small uninsulated area only 2 to 3

ow through the membrane about 5000-fold. At the

This sub-

Schwann cell rotates around the axon many times,

rst envelops the axon. Then the

Schwann cells in the following manner: The membrane

The myelin sheath is deposited around the axon by

of Ranvier.

than the axon itself. About once every 1 to 3 milli-

uid. Surrounding

action potential. The axon is

ber. The

Figure 5

bers.

The average nerve trunk

the large ones. The large

cross-sectional area. However, a more careful look

many large nerve

shows a cross section of a typical small nerve, revealing

Figure 5

Myelinated and Unmyelinated Nerve Fibers.

in Nerve Trunks

of Signal Transmission

suddenly, a new action potential results, and the

for excitation. Then,

gure, thereby allowing the membrane potential again

state of hyperpolarization) gradually disappears, as

occur. But the excess potassium conductance (and the

long as this state exists, self

14.As

also shown in Figure 5

nearer to the potassium Nernst potential.This is a state

tial is over, thus drawing the membrane potential

negativity than would otherwise occur. This continues

membrane, leaving inside the

Membrane Physiology, Nerve, and Muscle

Unit II

fiber considerably more

for nearly a second after the preceding action poten-

called hyperpolarization,

–

–re-excitation will not

shown after each action potential is completed in the
fi
to increase up to the threshold

process occurs again and again.

Special Characteristics

–15

fibers that constitute most of the

reveals many more very small fibers lying between

fibers are myelinated, and the

small ones are unmyelinated.
contains about twice as many unmyelinated fibers as
myelinated fi

–16 shows a typical myelinated fi

central core of the fiber is the axon, and the membrane
of the axon is the membrane that actually conducts the

filled in its center with axo-

plasm, which is a viscid intracellular fl
the axon is a myelin sheath that is often much thicker

meters along the length of the myelin sheath is a node

of a Schwann cell fi

laying down multiple layers of Schwann cell membrane
containing the lipid substance sphingomyelin.
stance is an excellent electrical insulator that decreases
ion fl
juncture between each two successive Schwann cells

micrometers in length remains where ions still can flow
with ease through the axon membrane between the
extracellular fluid and the intracellular fluid inside the

Even though almost no ions can flow through the thick

flow with

potentials occur

–

saltatory conduction.

electrical current flows through the surrounding extra-
cellular fluid outside the myelin sheath as well as
through the axoplasm inside the axon from node to

Cross section of a small nerve trunk containing both myelinated

Figure 5–15

and unmyelinated fibers.

Axon

Node of Ranvier

Unmyelinated axons

Schwann cell nucleus

Schwann cell cytoplasm

Schwann cell

nucleus

Schwann cell

cytoplasm

Myelin

sheath

from Leeson TS, Leeson R: Histology. Philadelphia: WB Saunders,

unmyelinated nerve fibers (shown in cross section). (

the membrane and cytoplasm of a Schwann cell around multiple

Partial wrapping of

myelin sheath of the myelinated nerve fiber.

of a Schwann cell membrane around a large axon to form the

Wrapping

Figure 5–16

Function of the Schwann cell to insulate nerve fibers. A,

A, Modified

1979.)

subthreshold potentials.

fail to elicit an action potential, they are called

acute local potentials,

after both of these weak stimuli. These local potential

The stimulus does, however, disturb the membrane

ulus is greater, but again, the intensity is still not enough.

of the action potential to develop. At point B, the stim-

85 millivolts, but this is not a suf

stimulus at point A causes the membrane potential to

applied stimuli of progressing strength. A very weak

take place. Figure 5

increased, there comes a point at which excitation does

ber. However, when the voltage of the stimulus is

it. This causes a state of hyperpolarization, which actu-

electrode, the injection of positive charges on the

ing in an action potential. Conversely, at the positive

brane and allows the sodium channels to open, result-

This decreases the electrical voltage across the mem-

ber.

cal voltage across the membrane. That is, negative

voltage-gated sodium channels. Further, these channels

The cause of this effect is the following: Remember

electrode.

the other positively charged. When this is done, the

electrodes, one of which is negatively charged and

The usual means for exciting a nerve or

Excitation of a Nerve Fiber by a Negatively Charged Metal

the excitation process, let us begin by discussing the

heart and intestine. For the purpose of understanding

neuron to the next in the brain, and electrical current to

to elicit nerve or muscle action potentials: mechanical

brane. All these are used at different points in the body

membrane, or passage of

chemical

disturbance of the membrane,

mechanical

the sodium channels. This can result from

Basically, any factor that causes sodium ions to begin to

Excitation—The Process

bers.

The velocity of con-

Velocity of Conduction in Nerve Fibers.

ization to occur with very little transfer of ions.

bers is the following: The excellent

impulses.

essary, and therefore requiring little metabolism for re-

because only the nodes depolarize, allowing perhaps

bers as much as 5- to 50-fold. Second,

ber, this mecha-

Saltatory conduction is of value for two reasons. First,

saltatory.

ber, which is the

Membrane Potentials and Action Potentials

Chapter 5

the nerve impulse jumps down the fi
origin of the term “

”

by causing the depolarization process to jump long
intervals along the axis of the nerve fi
nism increases the velocity of nerve transmission in
myelinated fi
saltatory conduction conserves energy for the axon

100 times less loss of ions than would otherwise be nec-

establishing the sodium and potassium concentration
differences across the membrane after a series of nerve

Still another feature of saltatory conduction in

large myelinated fi
insulation afforded by the myelin membrane and the 50-
fold decrease in membrane capacitance allow repolar-

duction in nerve fibers varies from as little as 0.25 m/sec
in very small unmyelinated fibers to as great as 100 m/
sec (the length of a football field in 1 second) in very
large myelinated fi

of Eliciting the Action
Potential

diffuse inward through the membrane in sufficient
numbers can set off automatic regenerative opening of

effects on the

electricity through the mem-

pressure to excite sensory nerve endings in the skin,
chemical neurotransmitters to transmit signals from one

transmit signals between successive muscle cells in the

principles of electrical stimulation.

Electrode.

muscle in the experimental laboratory is to apply elec-
tricity to the nerve or muscle surface through two small

excitable membrane becomes stimulated at the negative

that the action potential is initiated by the opening of

are opened by a decrease in the normal resting electri-

current from the electrode decreases the voltage on the
outside of the membrane to a negative value nearer to
the voltage of the negative potential inside the fi

outside of the nerve membrane heightens the voltage
difference across the membrane rather than lessening

ally decreases the excitability of the fiber rather than
causing an action potential.

Threshold for Excitation, and “Acute Local Potentials.”

A weak

negative electrical stimulus may not be able to excite a
fi

–18 shows the effects of successively

change from –90 to –

fi-

cient change for the automatic regenerative processes

potential locally for as long as 1 millisecond or more

changes are called

and when they

acute

Myelin sheath

Node of Ranvier

Axoplasm

current from node to node is illustrated by the arrows.

Saltatory conduction along a myelinated axon. Flow of electrical

Figure 5–17

Milliseconds

Millivolts

Threshold

Acute

subthreshold

potentials

Action potentials

stimuli are below the threshold value required for eliciting an

Note development of “acute subthreshold potentials” when the

Effect of stimuli of increasing voltages to elicit an action potential.

Figure 5–18

action potential.

the electron beam is moved across the screen, the spot

uorescent material glows. If

hit the screen surface, the

red. Where the electrons

ray oscilloscope. The cathode ray tube itself is composed

Figure 5

the cathode ray oscilloscope.

extremely rapidly. For practical purposes, the only

recording these potential changes. However, it must be

of this chapter, an electrical meter has been shown

takes place in less than 1/1000 second. In some

during the course of an action potential. Indeed, most

Earlier in this chapter, we noted

Recording Membrane

fail to pass along the anesthetized nerves.

) is reduced below 1.0, nerve impulses

open, thereby reducing membrane excitability. When

nels, making it much more dif

tetracaine.

thetics, including

stabilizer.

excitability. Therefore, calcium ions are said to be a

For instance,

decrease excitability.

membrane-stabilizing factors, can

ity, still others, called

and Local Anesthetics

Inhibition of Excitability

Therefore, one can readily calculate that such a

This period for

cannot be elicited, even with a strong stimulus, is

The period during which a second action potential

nels open, and a new action potential can be initiated.

fraction of a second, the inactivation gates of the chan-

membrane potential level. Then, within another small

at this point will open the inactivation gates. The only

(or calcium channels, or both) become inactivated, and

after the action potential is initiated, the sodium channels

ceding action potential. The reason for this is that shortly

Stimulus Cannot Be Elicited

Potential, During Which a New

After an Action

old level before the action potential is set off.

lus causes a local potential change at the membrane, but

Thus, this

acute local potential is also stronger, and the action

At point D, the stimulus is still stronger, the

level required to elicit an action potential, called the

stronger. Now the local potential has barely reached the

18, the stimulus is even

At point C in Figure 5

Membrane Physiology, Nerve, and Muscle

Unit II

–

threshold level, but this occurs only after a short “latent
period.”

potential occurs after less of a latent period.

figure shows that even a very weak stimu-

the intensity of the local potential must rise to a thresh-

“Refractory Period”

A new action potential cannot occur in an excitable fiber
as long as the membrane is still depolarized from the pre-

no amount of excitatory signal applied to these channels

condition that will allow them to reopen is for the mem-
brane potential to return to or near the original resting

called the absolute refractory period.
large myelinated nerve fibers is about 1/2500 second.

fiber

can transmit a maximum of about 2500 impulses per
second.

—

“Stabilizers”

In contrast to the factors that increase nerve excitabil-

a high extracellular

fluid calcium ion concentration decreases membrane
permeability to sodium ions and simultaneously reduces

“

”

Local Anesthetics.

Among the most important stabilizers

are the many substances used clinically as local anes-

procaine and

Most of these

act directly on the activation gates of the sodium chan-

ficult for these gates to

excitability has been reduced so low that the ratio of
action potential strength to excitability threshold (called
the “safety factor”

Potentials and Action
Potentials

Cathode Ray Oscilloscope.

that the membrane potential changes extremely rapidly

of the action potential complex of large nerve fibers

figures

understood that any meter capable of recording most
action potentials must be capable of responding

common type of meter that is capable of responding
accurately to the rapid membrane potential changes is

–19 shows the basic components of a cathode

basically of an electron gun and a fluorescent screen
against which electrons are fi

Vertical

Electrical

stimulator

Electronic

sweep circuit

Horizontal

plates

Electron gun

Plugs

Nerve

Electronic

amplifier

Recorded

action potential

Electron

beam

Stimulus

artifact

Cathode ray oscilloscope for recording transient

Figure 5–19

action potentials.

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Ruff RL: Neurophysiology of the neuromuscular junction:

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Alberts B, Johnson A, Lewis J, et al: Molecular Biology of

the recorded action potential itself.

nerve action potential. Then further to the right is

changes from the nerve electrodes shown vertically.

gure, giving a time base horizontally and voltage

electronic circuit of the oscilloscope. This gives the

nerves. The beam of electrons also is swept horizontally

tioned above and below. Appropriate electronic control

two sides of the electron beam, and the other set posi-

surface, the cathode ray tube is provided with two sets

Membrane Potentials and Action Potentials

Chapter 5

of glowing light also moves and draws a fluorescent line
on the screen.

In addition to the electron gun and fluorescent

of electrically charged plates—one set positioned on the

circuits change the voltage on these plates so that the
electron beam can be bent up or down in response to
electrical signals coming from recording electrodes on

across the screen at a constant time rate by an internal

record shown on the face of the cathode ray tube in
the fi

Note at the left end of the record a small stimulus arti-
fact caused by the electrical stimulus used to elicit the

References

Springfi

membrane current and its application to conduction and

fication in inward-rectifier K

2003.