DEPARTMENT OF PHYSIOLOGY

FACULTY OF BASIC MEDICAL SCIENCES

COLLEGE OF HEALTH SCIENCES
USMANU DANFODIYO UNIVERSITY, SOKOTO

PHL4201: HUMAN PHYSIOLOGY

(EXCITABLE TISSUES AND ANS)

DR. LADAN KABIR.

 INTRODUCTION:
 Excitable tissues are cells/tissues that are capable of
generating Action Potential when their Resting
Membrane Potential is disturbed.
 These change in membrane potential generates
electrochemical impulse which are used to transmit
cell signals or activate functions within the body.
 All cells in the body are in a state of resting and

are said to have a resting membrane potential,

however not all cell are capable of being excited,

 Those cells that are excitable has the following

characteristics:
• Unequal distribution of one or more species of
ion.

• Their membrane must be permeable to one or

more of those ions.

• Excitable tissues includes; Skeletal, Smooth
and Cardiac muscles and Nerves.
• RMP occur due to the fact that the body is in a neutral

state, i.e. the number of cation is almost equal to that

of anion both in the ICF and ECF.

• They are a number of channels in the cell membranes

which help to achieve such, and in the initiation of AP.

this includes;
• Leakey channels
• Protein phosphorylation/ electrogenic pump
or Na+/k+ ATPase
• Ligand gated channels
• Voltage gated channels
• Pressure gated channels
• Naturally the cell try to make its surrounding salty

compared to its interior, resulting in ECF to have

high concentration of Na+ and the ICF has more k+.

• And the cell is continuously moving Na+ out

against its concentration gradient uphill diffusion.

 RESTING MEMBRANE POTENTIAL
 OUTLINE:
• Active transport of Na+/K + through cell
membrane
• Diffusion potential
• Nernst potential and Goldman formula
• Origin and contributors to Normal Resting
Membrane Potential
• Clinical physiology
 Na+/K+ pump

• Active Transport of Na+/K+ through membranes of

excitable cell by a powerful Na+/K+ pump that continually

transports sodium ions to the outside of the cell and

potassium ions to the inside,

• this is an electrogenic pump because more positive

charges are pumped to the outside than to the inside

(3Na+ ions to the outside for each 2K+ ions to the inside)
• leaving a net deficit of positive ions on the inside;

• this causes a negative potential inside the cell

membrane of about -4mV.

• The Na+/K+ pump also causes large concentration

gradients for sodium and potassium across the resting

nerve membrane. These gradients are the following:

• Ion Inside Outside Unit

• K 140 4 mEq/L or mmol/L

• Na 14 142 mEq/L or mmol/L

• Diffusion Potential is a potential difference that

build in a cell as a result of an ion concentration

Difference between two sides of the membrane due

to diffusion of the ion through its concentration

gradient from inside to outside of the cell.

• Diffusion Potential of K+

• If K concentration is great inside a cell but very low outside, and let

assume that the membrane is permeable to only K, because of the

large potassium concentration gradient from inside to outside,

• there is a strong tendency for extra numbers of potassium ions to

diffuse outward through the membrane via the K + Leakey

channels.
• As they do so, they carry positive electrical charges

to the outside thus creating electropositivity

outside the membrane

• And electronegativity inside because of negative

anions (protein and phosphate) that remain

behind and do not diffuse outward.

• The electronegativity created inside the cell as a

result of K diffusing outside the cell is called K+ DP,

• within a millisecond the potential difference between

the inside and outside (diffusion potential) becomes

great enough to block further net potassium diffusion

to the exterior, despite the cell still permeable to K+.

• This potential that prevent net diffusion of K+ is called

equilibrium potential i.e. the potential in which

equilibrium is achieved between its concentration

gradient and electrical gradient.

• In the normal mammalian Nerve fiber the potential

difference is about -85millivolts.

 Diffusion Potential of Na+

• Another instant where the membrane is highly permeable

to the sodium ions but impermeable to all other ions.

• Diffusion of the positively charged sodium ions to the inside

creates a membrane potential of opposite polarity to that

produce by K+, with negativity outside and positivity inside.

• Again, the membrane potential rises high enough within

milliseconds to block further net diffusion of Na+ to the

inside.

• The potential is about 60-65 millivolts positive inside.

• We see that a concentration difference of ions across a

selectively permeable membrane can, under appropriate

conditions, create a membrane potential.

 Nernst Potential (equilibrium potential)

• As the ions diffuses through the cell membrane, it

concentration build up and get to a level that

opposes the net diffusion of that particular ion

through the membrane and is called the Nernst

potential.
• Nernst potential is determined by the ratio of the

concentrations of that specific ion on the two sides of the

membrane.

• Nernst potential of potassium is the diffusion potential of

potassium in which net movement of potassium is zero in

spite of the fact that the membrane is still permeable to

potassium.
• EMF (millivolts) = ± 61 × log
Concentration inside
Concentration outside
 GOLDMAN HODGKIN KATZ FORMULA

• The Goldman formula is used to calculate the Nernst

potential when the cell is permeable to more than

one electrolyte and the most important electrolytes

are Sodium, potassium, and chloride and are also

involved in the development of membrane potentials.

• The concentration gradient of each of these

ions across the membrane helps determine

the voltage of the membrane potential and it’s

proportional to the membrane permeability

for that particular ion.

• That is, if the membrane has zero permeability to

both potassium and chloride ions, the membrane

potential becomes entirely dominated by the

concentration gradient of sodium ions alone, and

the resulting potential will be equal to the Nernst

potential for sodium.

• The same holds for each of the other two ions if the

membrane should become selectively permeable for

either one of them alone.

• when excess positive ions diffuse to the outside of a cell

due to their high concentration inside the cell , they carry

positive charges to the outside but leaves the

nondiffusible negative anions on the inside, thus creating

electronegativity on the inside

• The opposite effect occurs when there is a gradient

for a negative ion. Eg a chloride ion gradient from the

outside to the inside causes negativity inside the cell,

• because excess negatively charged chloride ions

diffuse to the inside, while leaving the nondiffusible

positive ions on the outside.

• The sodium and potassium channels undergoes

rapid changes during transmission of impulse,

whereas the permeability of the chloride channels

does not change greatly during this process because

the Nernst potential for chloride is around -85mV

which is also around the K diffusion potential.

• Therefore, rapid changes in sodium and potassium

permeability are primarily responsible for signal

transmission.

• Factors that contribute to the formation of Resting

Membrane Potential.
1. Contribution of the Na+-K+ Pump.
• The Na+-K+ pump is shown to provide an additional
contribution to the resting potential.
• There is continuous pumping of 3Na to the outside for each
2K pumped to the inside of the membrane, the fact that more
sodium ions are being pumped to the outside than potassium
to the inside causes continual loss of positive charges from
inside the membrane this creates the initial degree of
negativity (about –4to millivolts) on the inside beyond that
which can be accounted for by diffusion alone.
 2. Leakage of Potassium through cell Membrane.

• The cells has a channel protein sometimes called a “tandem pore

domain,” potassium channel, or potassium (K+) “leak” channel, in the

cell membrane through which potassium can leak even in a resting cell.

• These K+ leaky channels may also leak sodium ions slightly but are far

more permeable to potassium than to sodium, normally about 100 times

as permeable, this differential permeability is a key factor in determining

the level of the normal resting membrane potential.

3. Contribution of the Potassium Diffusion Potential.

• We assume that the only movement of ions through the

membrane is diffusion of potassium ions, Because of the high
ratio of potassium ions inside to outside, 35:1, the Nernst
potential corresponding to this ratio is −94 millivolts because the
logarithm of 35 is 1.54, and this multiplied by −61 millivolts is −94
millivolts.

• Therefore, if potassium ions were the only factor causing the

resting potential, the resting potential inside the fiber would be
equal to −94 millivolts.
4. Contribution of Sodium Diffusion Potential.
• When there is slight permeability of the cell membrane
to sodium ions, caused by the minute diffusion of
sodium ions through the K+/Na+ leak channels.
• The ratio of sodium ions from inside to outside the
membrane is 0.1, and this gives a calculated Nernst
potential for the inside of the membrane of +61
millivolts.
• If the membrane is highly permeable to potassium
but only slightly permeable to sodium, it is logical
that the diffusion of potassium contributes far more
to the membrane potential than does the diffusion
of sodium.
• Remember In the normal nerve fiber, the
permeability of the membrane to potassium is about
100 times as great as its permeability to sodium.
• Using this value in the Goldman equation gives a

potential inside the membrane −86 millivolts,

which is near the potassium equilibrium potential.

• Therefore, the net membrane potential with all

these factors operative at the same time is about

−90 millivolts.
• In summary, the diffusion potentials alone caused by
potassium and sodium diffusion would give a membrane
potential of about −86 millivolts, almost all of this being
determined by potassium diffusion.
• Then, an additional −4 millivolts is contributed to the
membrane potential by the continuously acting
electrogenic Na+/K+ pump, giving a net membrane
potential of −90 millivolts.
 Clinical physiology

• Resting Membrane Potential is important physiologically because

it determine the electrical properties of a resting cell.

• The most important electrolyte which determine such being K

and the normal value for serum K (kalemia) is 3.5 -5.5 Mmol/l.

• they are a number of factors that may increase or decrease the

level of K in the body, however K is regulated at the level of
absorption and excretion not intake, so even if someone take
excess K orally he is less likely to come up with high blood level of
K.
 Causes of high K level

• Acute kidney injury

• Chronic kidney failure

• Addison’s disease

• Alcoholism

• Diuretics

• Destructions of RBC due to severe injury or burns

• Massive tissue damage

• Type 1 diabetes
 Causes of low K level

• Chronic kidney disease

• Diabetic ketoacidosis

• Diarrhea

• Vomiting

• Primary aldosteronism

• Folic acid deficiency

• Some antibiotics
 Effect of low level of K in the blood on membrane potential:

• When serum/blood level of K is below 3.5Mmol/l it is called

Hypokalemia and K will tend to diffuse to the ECF to replace
the lost K, leaving behind non diffusible anions, this will shift
the resting membrane potential to become more negative
(away from the threshold potential)

• hyperpolarization, and the cell will become difficult to be

excited and all the electrical activities of the body will be
affected especially in excitable cell.
 Effect of high level of K in the blood on membrane
potential:
• When serum K level is above 5.5Mmol/l it is called
Hyperkalemia, the intracellular K diffusion through leaky
channels will reduce and the membrane will become
less negative or slightly polarize (toward the threshold
potential).
• The net effect will be inhibition of voltage gated Na
channels, and the cell become less excitable.
• Thus both hypo and hyper kalemia causes difficulty in
exciting the cell both in different mechanism, both hypo
and hyper are deadly however hyperkalemia has some
medical importance when use as cardioplegic
substance.

• Hypernatremia or hyponatremia has no effect on the

RMB because the resting cell is not permeable to
sodium.
 ACTION POTENTIAL

 OUTLINE;

• Definition.

• Stages.

• Initiation.

• Threshold of initiation.

• Mechanism, propagation and transmission.

 Definitions;

• AP are rapidly developing membrane potential difference

which rapidly travels over the membrane or are

electrochemical fluctuation in the membrane of excitable

cells.

• They are rapid changes in the membrane potential that

spread rapidly along the nerve fiber membrane.

• AP are electrochemical changes occurring in the membrane of
excitable cell which rapidly propagate.

• Nerve signals are transmitted by action potentials, 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.

• To conduct a nerve signal, the action potential moves along

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

• Although AP last for a very short time (milliseconds) it is

categorized into stages which includes;

• Resting Stage. This is the resting membrane potential

before the action potential begins. The membrane is said to
be “polarized” during this stage, this is because of the -85 to
−90 millivolts negative membrane potential that is present.
 Depolarization Stage.

• At this time, the membrane suddenly becomes permeable to sodium

ions, allowing tremendous numbers of positively charged sodium ions

to diffuse to the interior of the axon.

• The normal “polarized state of −90 millivolts is immediately neutralized

by the inflowing positively charged sodium ions, with the potential

rising rapidly in the positive direction. This is called depolarization.

• In large nerve fibers, the great excess of positive sodium ions moving

to the inside causes the membrane potential to actually “overshoot”

beyond the zero level and to become somewhat positive.

 Repolarization Stage.

• Within 1/10,000 of a second, after the membrane

becomes highly permeable to sodium ions, the sodium

channels begin to close and the potassium channels open

more than normal.

• Then, rapid diffusion of potassium ions to the exterior re-

establishes the normal negative resting membrane

potential.
 Initiation of the Action Potential
• As long as the membrane of the nerve fiber
remains undisturbed, no action potential will
occurs, if any event causes enough initial rise in
the membrane potential from −90 millivolts
toward the zero level, the rising voltage itself
causes many voltage-gated sodium channels to
begin opening.
• This allows rapid inflow of sodium ions, which causes a
further rise in the membrane potential, thus opening still
more voltage-gated sodium channels and allowing more
streaming of sodium ions to the interior of the cell.
• This process is a positive-feedback cycle that, once the
feedback is strong enough, continues until all the voltage
gated sodium channels have become activated (opened).
• Then, within another fraction of a millisecond,

the rising membrane potential causes closure

of the sodium channels and opening of

potassium channels and the action potential

soon terminates.
 Threshold for Initiation of the Action Potential.

• Action potential will not occur until the initial rise in

membrane potential is great enough to create a

positive feedback, This occurs when the number of

Na+ ions entering the cell becomes greater than the

number of K+ ions leaving the cell.

• A sudden rise in membrane potential of 15 to 30
millivolts is usually required.
• Therefore, a sudden 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 potential.
• This level of −65 millivolts is said to be the threshold
for stimulation of that nerve fiber.
 Mechanism

• The cell will remain in it resting state with resting membrane

potential until an external force act on it depending on the
receptor present in the cell,

• those receptors usually open pressure gated channels in the

cell membrane and result in Na influx and shift the
electronegativity of the resting membrane potential to a
certain potential (threshold potential) and this will open
voltage-gated sodium channel.
• This channel has two gates—one near the outside
of the channel called the activation gate, and
another near the inside called the deactivation gate
during normal resting membrane when the
membrane potential is −90 millivolts.
• In this state, the activation gate is closed, which
prevents any entry of sodium ions to the interior of
the cell through these sodium channels.
• When the Membrane potential becomes less
negative than during the resting state, rising from
−90 millivolts toward zero,
• it finally reaches a voltage—usually somewhere
between −70 and −50 millivolts—that causes a
sudden conformational change in the activation
gate, flipping it all the way to the open position.
• This is called the activated state;
• during this state, sodium ions can pour inward through the channel,

increasing the sodium permeability of the membrane as much as 500-

to 5000-fold.

• The same increase in voltage that opens the activation gate also

closes the inactivation gate.

• The Inactivation gate, however, closes a few seconds after the

activation gate opens. That is, the conformational change that flips the

inactivation gate to the closed state is a slower process than the

conformational change that opens the activation gate.

• Therefore, after the sodium channel has remained open for a few

millisecond, the inactivation gate closes, and sodium ions no

longer can pour to the inside of the membrane.

• At this point, the membrane potential begins to recover back

toward the resting membrane state, which is the repolarization
process.

• 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 potential level.
• Therefore, it is usually not possible for the sodium

channels to open again without first repolarizing the

cell.

• During the resting state, the gate of the potassium

channel is closed and potassium ions are prevented

from passing through this channel to the exterior.

• When the membrane potential rises from −90 millivolts
toward zero, this voltage change causes a
conformational opening of the gate and allows
increased potassium diffusion outward through the
channel.
• However, because of the slight delay in opening of the
potassium channels, for the most part, they open just
at the same time that the sodium channels are
beginning to close because of inactivation.
• Thus, the decrease in sodium entry to the cell and
the simultaneous increase in potassium exit from
the cell combine to speed the repolarization
process, leading to full recovery of the membrane
potential,
• These two voltage-gated channels are in addition
to the Na+-K+ pump and the K+ leak channels are
responsible for AP, however other factors include
 1. Negatively charged ions that cannot go through the

membrane channels include the anions of protein molecules

and many organic phosphate and sulfate compounds.

• Because these ions cannot leave the interior of the axon, any

deficit of positive ions inside the membrane leaves an excess of

these impermeant negative anions.

• Therefore, these impermeant negative ions are responsible for

the negative charge inside the fiber when there is a net deficit

of positively charged potassium ions and other positive ions.

2. Calcium Ions.

 The membranes of almost all cells of the body have a calcium

pump similar to the sodium pump, and calcium serves along with

(or instead of) sodium in some cells to cause most of the action

potential.

 Like the sodium pump the calcium pump transports calcium ions

from the interior to the exterior of the cell membrane (or into

the endoplasmic reticulum of the cell), creating a calcium ion

gradient of about 10,000-fold.

• This leaves an internal cell concentration of calcium
ions of about 10−7 molar, in contrast to an external
concentration of about 10−3 molar. In addition, there
are voltage-gated calcium channels.
• Because calcium ion concentration is more than
10,000 times greater in the extracellular than the
intracellular fluid, there is a tremendous diffusion
gradient for passive flow of calcium ions into the cells.
• These channels are slightly permeable to sodium
ions and calcium ions, but their permeability to
calcium is about 1000-fold greater than to
sodium under normal physiological conditions.
• When they open in response to a stimulus that
depolarizes the cell membrane, calcium ions flow
to the interior of the cell.
• A major function of the voltage-gated calcium ion
channels is to contribute to the depolarizing phase on
the action potential in some cells.
• The gating of calcium channels, however, is slow,
requiring 10 to 20 times as long for activation as for the
sodium channels.
• For this reason they are often called slow channels, in
contrast to the sodium channels, which are called fast
channels.
• Therefore, the opening of calcium channels provides a more
sustained depolarization, whereas the sodium channels play
a key role in initiating action potentials.

• Calcium channels are numerous in both cardiac muscle and

smooth muscle.

• In fact, in some types of smooth muscle, the fast sodium

channels are hardly present;

• therefore, the action potentials are caused almost entirely

by activation of slow calcium channels.
 Propagation of AP

• An action potential elicited at any one point on an

excitable membrane usually excites adjacent

portions of the membrane, resulting in

propagation of the action potential along the

membrane. This mechanism is as follows:

• A normal resting cell when excited at midportion

suddenly develops increased permeability to sodium,

there is flow of current from the depolarized areas of
the membrane to the adjacent resting membrane areas.

• That is, positive electrical charges are carried by the

inward-diffusing sodium ions through the depolarized

membrane and then for several millimeters in both
directions along the core of the axon.
• These positive charges increase the voltage for
a distance of 1 to 3 millimeters inside the large
myelinated fiber to above the threshold
voltage value for initiating an action potential.
• Therefore, the sodium channels in these new
areas immediately open and the explosive
action potential spreads.
• These newly depolarized areas produce still more local
circuits of current flow farther along the membrane,
causing progressively more and more depolarization.
• Thus, the depolarization process travels along the
entire length of the fiber.
• This transmission of the depolarization process along a
nerve or muscle fiber is called a nerve or muscle
impulse.
• Action potential travels in all directions away

from the stimulus until the entire membrane

has become depolarized

 All-or-Non Principle.

• Once an action potential has been elicited at any point on

the membrane of a normal fiber, the depolarization

process travels over the entire membrane if conditions are

right, or it does not travel at all if conditions are not right.

• This is called the all-or-non principle, and it applies to all

normal excitable tissues.

• Occasionally, the action potential reaches a point on the
membrane at which it does not generate sufficient voltage
to stimulate the next area of the membrane.

• When this occurs, the spread of depolarization stops.

Therefore, for continued propagation of an impulse to
occur, the ratio of action potential to threshold for
excitation must at all times be greater than

• 1. This “greater than 1” requirement is called the safety

factor for propagation.
 Reestablishing Membrane Potential
• The transmission of AP reduces slightly the
concentration differences of sodium and
potassium inside and outside the membrane
sodium ions diffuse to the inside during
depolarization and potassium ions diffuse to
the outside during repolarization.
• Therefore for AP to reoccur it becomes necessary to re-

establish the sodium and potassium membrane concentration

differences.

• This is achieved by action of the Na+-K+ pump to

establishment the original resting potential.

• That is, sodium ions that have diffused to the interior of the
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+ pump.
• Because this pump requires energy it is
considered to be an active metabolic process,
using energy derived from the adenosine
triphosphate (ATP) energy system of the cell.
• A special feature of the Na+-K+ ATPase pump is
that its degree of activity is strongly stimulated
when excess sodium ions accumulate inside the
cell membrane.
• In fact, the pumping activity increases
approximately in proportion to the third
power of this intracellular sodium
concentration.
• That is if Na concentration double the pump
activity increases about eightfold.
 Plateau in Some AP
• In some instances, the excited membrane does not
repolarize immediately after depolarization;
• instead, the potential remains on a plateau near the
peak of the spike potential for many milliseconds,
and only then does repolarization begins.
• The plateau help prolongs the period of
depolarization.
• This type of action potential occurs in heart muscle
fibers, 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.
• The cause of the plateau is because, in heart muscle
two types of channels are involve in depolarization
process:
• (a) the usual voltage-activated sodium channels, called
fast channels, and
• (b) voltage-activated calcium-sodium channels, which
are slow to open and therefore are called slow channels.
• Opening of fast channels causes the spike portion of the action
potential, whereas the prolonged opening of the slow calcium-
sodium channels mainly allows calcium ions to enter the fiber,
which is largely responsible for the plateau portion of the action
potential.

• Also the voltage-gated potassium channels are slower than

usual to open, often not opening much until the end of the
plateau.

• This delays the return of the membrane potential toward its

normal negative value of −80 to −90 millivolts
 Rhythmicity in some Excitable tissues

• Repetitive self-induced discharges of AP occur normally in the

heart, most smooth muscle, and in many of the neurons of
the central nervous system.

• These rhythmical discharges cause

(1) the rhythmical beat of the heart,

(2) rhythmical peristalsis of the intestines, and

(3) such neuronal events as the rhythmical control of

breathing.
• For spontaneous rhythmicity to occur,

• the membrane 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 membrane
depolarization.

• For example the resting membrane potential in the rhythmical

control center of the heart is only −60 to −70 millivolts.

• This is not enough negative voltage to keep the sodium and

calcium channels totally closed.

• Therefore, the following sequence occurs:

(1) Some sodium and calcium ions flow inward;

(2) This increases the membrane voltage in the

positive direction, which further increases
membrane permeability;

(3) still more ions flow inward

(4) The permeability increases more, and so on,

until an action potential is generated.
• Then, at the end of the action potential, the membrane repolarizes.

• After another delay of milliseconds or seconds, spontaneous excitability

causes depolarization again and a new action potential occurs

spontaneously.

• This cycle continues over and over and causes self-induced rhythmical

excitation of the excitable tissue.

• Toward the end of each action potential, and continuing for a short

period thereafter, the membrane becomes more permeable to

potassium ions.
• The increased outflow of potassium ions carries
tremendous numbers of positive charges to the outside
of the membrane, leaving inside the fiber considerably
more negativity than would otherwise occur.
• This continues for nearly a second after the preceding
action potential is over, thus drawing the membrane
potential nearer to the potassium Nernst potential,
which lead to a state called hyperpolarization,
• As long as this state exists, self-re-excitation will not
occur, but the increased potassium conductance
(and the state of hyperpolarization) gradually
disappears, thereby allowing the membrane
potential again to increase up to the threshold for
excitation.
• Then, suddenly, a new action potential results and
the process occurs again and again
• The central core of the fiber is the axon, and the
membrane of the axon is the membrane that actually
conducts the action potential the axon is filled in its
center with axoplasm, which is a viscid intracellular
fluid.
• Surrounding the axon is a myelin sheath that is often
much thicker than the axon itself.
• About once every 1 to 3 millimeters along the length of
the myelin sheath is a node of Ranvier.
• The myelin sheath is deposited around the axon by Schwann
cells in the following manner:

• The membrane of a Schwann cell first envelops the axon.

• Then the Schwann cell rotates around the axon many times,
laying down multiple layers of Schwann cell membrane
containing the lipid substance sphingomyelin.

• This substance is an excellent electrical insulator that

decreases ion flow through the membrane about 5000-fold.
• At the juncture between each two successive Schwann cells along the

axon, a small uninsulated area only 2 to 3 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 axon. This area is called the node of Ranvier.

• The large fibers are myelinated, and the small ones are unmyelinated

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

• Even though almost no ions can flow through the
thick myelin sheaths of myelinated nerves, they
can flow with ease through the nodes of Ranvier.
• Therefore, action potentials occur only at the
nodes. Yet the action potentials are conducted
from node to node,
• And this is called saltatory conduction.
• The nerve impulse jumps along the fiber from node to node, Saltatory

conduction is of two value

1. Increase the velocity of nerve transmission in myelinated fibers as much as 5-

to 50-fold.

2. Conserves energy for the axon because only the nodes depolarize, allowing

perhaps 100 times less loss of ions than would otherwise be necessary, and

therefore requiring little metabolism for re-establishing the sodium and

potassium concentration differences across the membrane after a series of nerve

impulses.
• The velocity of action potential conduction in nerve fibers

varies from as little as 0.25 m/sec in small unmyelinated

fibers to as great as 100 m/sec (the length of a football field

in 1 second) in large myelinated fibers

• Basically, any factor that causes sodium ions to begin to

diffuse inward through the membrane in sufficient numbers

can cause the sodium channels to open.

• This can result from mechanical disturbance of the membrane,
chemical effects on the membrane, or passage of electricity through
the membrane.

• All these are used at different points in the body to elicit nerve or
muscle action potentials:

• mechanical pressure to excite sensory nerve endings in the skin,

• chemical neurotransmitters to transmit signals from one neuron to

the next in the brain,

• and electrical current to transmit signals between successive muscle

cells in the heart and intestine.
 Threshold for Excitation, and “Local Potentials.”
• A weak negative electrical stimulus may not be able to
excite a cell.
• However, when the voltage of the stimulus is increased,
there comes a point at which excitation does take place.
• A weak stimulus A can causes the membrane potential to
change from −90 to −85 millivolts, but this is not a
sufficient change for the automatic regenerative
processes of the action potential to develop.
• The stimulus B is greater, but again, the intensity is still
not enough.
• The stimulus does, however, disturb the membrane
potential locally for as long as 1 millisecond or more
after both of these weak stimuli.
• These local potential changes are called acute local
potentials, and when they fail to elicit an action
potential, they are called acute subthreshold potentials.
• Shortly after the action potential is initiated, the
sodium channels (or calcium channels, or both)
become inactivated and no amount of excitatory
signal applied to these channels at this point will
open the inactivation gates.
• The only condition that will allow them to reopen
is for the membrane potential to return to or near
the original resting membrane potential level.
• Then, within another small fraction of a second, the inactivation gates

of the channels open and a new action potential can be initiated.

• The period during which a second action potential cannot be elicited,

even with a strong stimulus, is called the absolute refractory period.

• This period for large myelinated nerve fibers is about 1/2500 second.

• Therefore, one can readily calculate that such a fiber can transmit a

maximum of about 2500 impulses per second.

 Why AP?

• In contrast to the factors that increase nerve excitability, still

others, called membrane-stabilizing factors, can decrease

excitability.

• For instance, a high extracellular fluid calcium ion

concentration decreases membrane permeability to sodium

ions and simultaneously reduces excitability.

• Therefore, calcium ions are said to be a “stabilizer.”

• when calcium is deficiency and calcium ion
concentration fall to 50 percent below normal
spontaneous discharge occurs in some
peripheral nerves, often causing muscle
“tetany.”
• This is sometimes lethal because of tetanic
contraction of the respiratory muscles.
 Local Anesthetics.

• Among the most important stabilizers are the many substances used

clinically as local anesthetics, including procaine lidocaine and tetracaine.

• Most of these act directly on the activation gates of the sodium channels,

making it much more difficult for these gates to open, thereby reducing

membrane excitability.

• When excitability has been reduced so low that the ratio of action

potential strength to excitability threshold (called the “safety factor”) is

reduced below 1.0, nerve impulses fail to pass along the anesthetized