Useful to students

1. Graded Potential

2. Graded Potentials
➢Short-lived, local changes in membrane potential
(either depolarizations or hyperpolarizations) is
called graded potential.
➢These are local changes in membrane potential that
can vary in magnitude depending on the strength
and duration of the stimulus
➢The stronger the stimulus, the more channels open,
the larger the magnitude of the graded potential.
➢The longer the stimulus, the longer channels stay
open, the longer the graded potential lasts.

3. ●Graded Potential spread by passive Current flow.
●Graded potentials die over short distances
●If strong enough, graded potentials trigger action
potentials
●These impulses are incremental and may be
excitatory or inhibitory. They occur at the
dendrite or soma.

5. ● The wave of depolarization or
hyperpolarization which moves
through the cell with a graded
potential is known as local current
flow.

6. Current Flow During a Graded Potential
Chapter 4 Principles of Neural and Hormonal
Communication
Human Physiology by Lauralee Sherwood ©2010
Brooks/Cole, Cengage Learning

7. Changes in Membrane Potential

8. Chapter 4 Principles of Neural
and Hormonal Communication
Human Physiology by Lauralee
Sherwood ©2010 Brooks/Cole,
Cengage Learning
Graded Potential
●Occurs in small, specialized region of excitable cell
membranes
●Magnitude of graded potential varies directly with the
magnitude of the triggering event

9. Examples of graded potentials are:
1)Receptor potential.
2)Post synaptic potential
3)Slow wave potential
4)End plate potential
5)Pace maker potential

10. Types of graded potential
• Graded potential is of two types. They are:
Excitatory postsynaptic potential
Inhibitory postsynaptic potentials
•Excitatory postsynaptic potential: A graded
potential depolarization is called excitatory
postsynaptic potential (EPSP).
• Inhibitory postsynaptic potentials: A graded
potential hyperpolarization is called an inhibitory
postsynaptic potentials (IPSP).
•They occur in the cell body and dendrites of the
neuron.

11. Movement of the graded potential
• Spread of a graded potential is by a
process known as passive flow.
• The gated channel opens and positive
charge enters the cell. This initial
temporary area of depolarisation (the
membrane potential becomes less
negative) is called the active area.

12. • Graded potentials don’t cause any real
effect unless they cause a secondary action
potential. In the cell, the location
where graded potentials occur (i.e. where
the gated channels are situated) is
immediately adjacent to the area where
action potentials are generated (usually the
axon hillock).

13. Graded Potentials
Voltage changes in graded
potentials are decremental,
the charge is quickly lost
through the permeable
plasma membrane
short- distance signal

14. • Graded potentials
travel through the
neuron until they reach
the trigger zone. If they
depolarize the
membrane above
threshold voltage (about
-55 mV in mammals), an
action potential is
triggered and it travels
down the axon.
Graded Potentials Above Threshold
Voltage Trigger Action Potentials

15. Action Potentials (APs)
•Action potential is defined as a sudden, fast,
transitory and propagating change of the
resting membrane potential.
•It is a rapid sequence of changes in the
voltage across a membrane.
•Action potential occurs when the membrane
potential of a specific cell rapidly rises and
falls.

16. Action Potentials (APs)
➢The AP is a brief, rapid large change in
membrane potential during which potential
reverses so that inside of the excitable cell
transiently becomes more +ve than the outside.
➢APs do not decrease in strength with distance so
serve as long distance signals.
➢Events of AP generation and transmission are
the same for skeletal muscle cells and neurons

17. Course of the Action Potential
●The action potential begins with a partial
depolarization [A].
●When the excitation threshold is reached there is
a sudden large depolarization [B].
●This is followed rapidly by repolarization [C] and
a brief hyperpolarization [D].
potential
(mV)
[A]
[B] [C]
[D] excitation threshold
Time (msec)
-70
+40
Membrane
0
0 1 2 3

18. Marked changes in membrane
permeability and ion movement lead to
an action potential (AP)
●Passive diffusion of K+ makes greatest contribution
to the RMP due to more permeability of plasma
membrane to K+ through leak
channels at rest.
●During an AP marked changes in membrane
permeability to Na+ and K+ take place
permitting rapid fluxes down their
electrochemical gradient
●These ions carry the current responsible for
the potential changes that occur during an
AP

19. ● Action potential takes place as a
result of the triggered opening
and subsequent closing of 2
specific types of channels
➢Voltage gated Na+ channels
➢Voltage gated K+ channels

20. ROLE OF VOLTAGE GATED Na+
CHANNEL & VOLTAGE GATED K+
CHANNELS IN ACTION POTENTIAL

21. Voltage gated Na+ channels
● Most important channels during AP
●It has two gates:
ACTIVATION GATES:
❖At RMP activation gates are closed so no Na+ influx
at RMP through these channels
❖These activation gates open when membrane
potential become less negative than during resting
state then the activation gates of these voltage gated
channels open so increasing Na+ permeability to 500-
5000 fold.

22. Inactivation gates
●The same increase in voltage that open the activation
gates also closes the inactivation gates but closing of
gates is a slower process than opening so large
amount of Na+ influx has occurred
●Another important feature of Na+ channels
inactivation is that the inactivation gate will not
reopen until the membrane potential returns to or
near the original RMP.

23. •.

24. Voltage gated K+ channel
●During RMP Voltage gated K+ channels are closed
●The same stimulus which open voltage gated Na+
channels also open voltage gated K+ channel
●Due to slow opening of these channels they open just
at the same time that the Na+ channels are beginning
to close because of inactivation.
●So now decrease Na+ influx and simultaneous
increase in K+ out flux cause membrane potential to
go back to resting state (recovery of RMP)
●These channels close when membrane potential
reaches back to RMP

25. •.

26. Phases of action potential
● Depolarization
● Repolarization
●Hyperpolarization

27. Depolarization (decrease in potential;
membrane less negative)
Repolarization (return to resting potential after
depolarization)
Hyperpolarization (increase in potential;
membrane more negative)

28. O
+60
+50
+40
->30
+20
"- +10
-10
-20
-30
—
40
-5
0
-6
0
-70
-80
—
90
Na”*
Na”° ! K
“
- - - - - - - - Threshold potential
Resting potential
0 2001 Brooks/Cole - Thomson Learning
Time (msec)

29. Initiation of action potential
●To initiate an AP a triggering event causes the
membrane to depolarize from the resting potential
of -90 mvs.
●Depolarization proceeds slowly at first until it
reaches a critical level known as threshold
potential. i.e. -65 mvs. At threshold explosive
depolarization occurs.
▪An AP will not occur until the initial rise in
membrane potential reaches a threshold level.
▪This occurs when no. of Na+ entering the
cell becomes greater than the no. of K+
leaving the cell.

30. Threshold and Action Potentials
Threshold Voltage– membrane is depolarized by
15 to 20 mV
Subthreshold stimuli produce subthreshold
depolarizations and are not translated into APs
Stronger threshold stimuli produce depolarizing
currents that are translated into action potentials
All-or-None phenomenon – action potentials
either happen completely, or not at all depending
on threshold

31. Passive spread of
current from adjacent
site already depolarized
Depolarization
(decrease in
Imembrane potential
Positive-f e e d b ac k c y c l e
Infl ux of Na”
(wh ich further decreases
membrane potential)
Opening of some
voltage-gatecl
N a * channels

33. Action Potential: Resting
State
+ +
Na and K channels are closed
Each Na+ channel has two voltage-regulated gates
Activation gates –
closed in the resting
state
Inactivation gates –
open in the resting
state
Depolarization opens the activation gate (rapid)
and closes the inactivation gate (slower) The gate
for the K+ is slowly opened with depolarization.

35. Depolarization Phase
Na+ activation gates open quickly and Na+ enters
causing local depolarization which opens more
activation gates and cell interior becomes
progressively less negative. Rapid depolarization and
polarity reversal.
Threshold – a critical level of depolarization
(-55 to -60 mV) where
depolarization becomes
self-generating
Positive Feedback?

37. Repolarization Phase
Sodium inactivation gates of Na+ channels close.
As sodium gates close, the slow voltage-sensitive K+
gates open and K+ leaves the cell following its
electrochemical gradient and the internal negativity of
the neuron is restored

39. Hyperpolarization
The slow K+ gates remain open longer than is needed
to restore the resting state. This excessive efflux causes
hyperpolarization of the membrane
The neuron is
insensitive to
stimulus and
depolarization
during this time

40. Depolarization increases the probability of
producing nerve impulses. Hyperpolarization
of producing nerve
reduces the probability
impulses.

41. Role of the Sodium-Potassium Pump
Repolarization restores the resting electrical
conditions of the neuron, but does not restore the
resting ionic conditions
Ionic redistribution is accomplished by the
sodium-potassium pump following
repolarization

42. Importance of Action Potential
Generation
●Nerve traffic, muscle contraction, hormone
release, G.I. secretions, Cognitive thought,
etc.
●Action Potentials are required for the
senses - Sight, hearing, and touch are all
dependent on action potentials for
transmission of information to the brain
●Threshold stimuli (Graded Potential) cause
the.generation of an action potential

44. Role of Calcium ions in Action
potential
●Calcium pump in almost all cells of the body
maintain the calcium gradient with high Ca in ECF
as compared to ICF.
●In addition to Ca pumps there are voltage gated Ca
channels which are slightly permeable to Na+ as well
as to Ca++ ions.
●So when they open both Na and Ca flow to the
interior of the fiber. So called Ca Na channels.
●They are slow to open requiring 20 times as long for
activation as Na channels so called slow channels in
contrast to Na channels which are fast channels.

45. ●Ca++ channels are numerous in smooth muscles and
cardiac muscle. In some smooth muscles the fast
Na+ channels are hardly present so that the AP are
caused almost entirely by activation of slow Ca++
channels.

46. Increased permeability of Na channels
when there is deficit of Ca ions
●The conc. Of Ca ions in ECF has profound effect on
the voltage level at which the Na channels become
activated.
●So when there is a deficit of Calcium ions in the
ECF the voltage gated Na channels open by very little
increase of MP from its normal very negative level.
so nerve fiber become highly excitable .
●When Ca levels fall 50% below normal spontaneous
discharge occurs in some peripheral nerves causing
tetany. Its lethal when respiratory muscles are
involved.

47. Cause:
●Ca bind to the exterior surface of the voltage gated
Na channels protein molecule.
●The +ve charge of Ca ions in turn alter the electrical
state of the channel protein itself.
●So altering the voltage level required to open the
sodium gates.

48. Propagation of
Action Potential
●A single action
potential involves
only a small portion
of the total excitable
cell membrane and
then the
potential is
propagating
action
self-
and
moves away from the
stimulus (point of
origin)

49. Direction of Action potential
●AP travels in all directions away from the stimulus
until the entire membrane is depolarized

50. Conduction of Action Potentials
● Two types of propagation
● Contiguous conduction
● Conduction in unmyelinated fibers
● Action potential spreads along every portion of the
membrane
● Saltatory conduction
● Rapid conduction in myelinated fibers
● Impulse jumps over sections of the fiber covered with
insulating myelin

51. Graded
potential
> threshold!,t
Active area at peak
ol action potential
-79
2001 Brooks/Cole - Tnomson Learning
Adjacent inactive area into
which depolarizat ion is
spreading: will soon reach
threshold
Remainder of axon
still at reating potential
LocaI current flow that
depolar izes adjacent inactive
area from rest ing to threshol d
Direction of propagation of action potential

52. Previous active area
returned to resting
potential
Adjacent area that
was brought to
threshold by local
current flow; now
active at peak of
action potential
New adjacent inactive
area into which
depolarization is
spreading: will soon
reach threshold
Remainder of axon
—50
6 2001 Brooks/Cole - Thomson Learning

53. Propagation of the AP
active andpaaahecurrent now
(1)
Na channels locally open in
response to stimulus generating
aFld aCtiOFl t«›teFltial
(Active, voltage-gated Na-• current)
Ma*‘ I!d@&h
Point A
I*)
Tke resulting innard current
J1O S p a s s i v o i y a l o r g t€lB BXOFI
Nat
channel
Peint B
Membrane
PROPAGATION
Point C

54. Propagation of the AP
actlvs and passive current flow
Point B
Membrane repolariud
Ptiint B
depolariud
Upstream Na• channels inactivate,
While K• channels open. Membrane
pDtential repolarizes. AXDFI is refractory here.
Locai d' DlarizatiDn causes
neighboring Nat channels to open
and generatRs Bn action potential
PROPAGATION
Pt1int C
resting

55. Nerve or muscle impulse
●The transmission of the depolarization process along
a nerve or muscle fibre is called impulse
●An action potential in the axon of a neuron is called a nerve
impulse and is the way neurons communicate.

56. Parts of neuron and signal
transmission in nerve trunks

57. Myelination
● Most mammalian axons are myelinated.
● The myelin sheath is provided by oligodendrocytes and
Schwann cells.

58. MYELIN
● Myelin
● Primarily composed of lipids sphingomyelin
● Formed by oligodendrocytes in CNS
● Formed by Schwann cells in PNS
• Myelin is insulating, preventing passage of ions
over the membrane as it is made up of lipids so
water soluble ions cannot permeate so current
cannot leak out in the ECF

59. Myelination
●In PNS each
Schwann cell
myelinates 1mm
of 1 axon by
wrapping round
& round axon
● Electrically
insulates axon

60. • The resistance of the
membrane to current leak
out of the cell and the
diameter of the axon
determine the speed of AP
conduction.
• Large diameter axons
provide a low resistance to
current flow within the axon
and this in turn, speeds up
conduction.
•Myelin sheath which wraps around vertebrate axons prevents current leak out of
the cells. Acts like an insulator, for example, plastic coating surrounding electric
wires. It is devoid of any passage ways.
• However, portions of the axons lack the myelin sheath and these are called
Nodes of Ranvier. They are present at about 1 mm intervals along the length
of axons . High concentration of Na+ channels are found at these nodes so AP
occurs only at nodes
2 ways to increase AP propagation speed

61. The action potentials
“jump” from node to
node.
Voltage-gated Na-r
channels are present
only at the nodes of
Ranvier

62. Saltatory Conduction (Saltere means jump
or leap) • When depolarization
reaches a node, Na+ enters
the axon through open
channels.
• At the nodes, Na+ entry
reinforces the depolarization
to keep the amplitude of the
AP constant
F8-22
• However, it speeds up again when the depolarization encounters the next node.
•The apparent leapfrogging of APs from node to node along the axon is called
saltatory conduction.
•Myelinated fibers conduct impulses about 50 times faster
than unmyelinated fibers of comparable size

63. •Saltatory conduction in myelinated fibers
from node to node
•As no ions can flow through myelin sheath they can
flow with ease through node of ranvier.
•Therefore, action potential or flow of electrical
currents occurs from node to node in a jumping
manner known as saltatory conduction

64. Importance of saltatory
conduction
through myelinated
•Increases the conduction velocity
nerve fiber.
•Conserves energy for the axon

65. of AP in myelina6d and
unmyelinated axon
Unmyelinated axon conduction : 0.5 to 10 mls
Myelinated axon conduclion up to 150 mls

66. Multiple Sclerosis
• In demylinating diseases, such as
multiple sclerosis, the loss of
myelin in the nervous system
slows down the conduction of APs.
Multiple sclerosis patients
complain of muscle weakness,
fatigue, difficulty with walking

67. Plateau in some action
potentials
●In cardiac muscle the excited muscle membrane
does not repolarize immediately after
depolarization ; instead the potential remains on a
plateau near the peak of the spike potential only
then does repolarization begins.
●Plateau prolongs the period of depolarization so
prolongs the contraction of heart muscle

68. Cause of plateau
● It is due to combination of factors:
1) First two types of channels causes depolarization
a)Voltage gated Na+ channels called fast channels for
spike potential
b)Slow Ca++ Na+ channels for plateau portion
2) The voltage gated K+ channels are slower than usual
to open, often not opening until the end of plateau
this delays the return of the MP towards normal
resting value

69. P^••••P
200 MU

70. The Action Potential Types

71. Rhythmicity of some excitable
tissues
●Repetitive self induced discharges occurs normally in
the heart , in most smooth muscles and in neurons of
the CNS.
● The rhythmical discharges causes:
1. Rhythmical beat of the heart
2.Rhythmical peristalsis of intestine
3. Rhythmical control of respiration

72. Re- excitation process necessary for
spontaneous rhythmicity
●For spontaneous rhythmicity to occur, the
membbrane even in its natural state must be
permeable enough to Na + ions or to Ca and Na thru
slow channels
●The resting membrane potential in the rhythmical
control center of the heart is only -60 - -70mvs
●This is not enough –ve voltage to keep the Na and Ca
channels totally closed .

73. ● So following sequence of events take place:
1. Some Na and Ca ions flow inside
2.This increases the membrane voltage in +ve
direction which further increases membrane
permeability .
3. Still more ions flow inside
4.+ve feed back mechanism
5.AP is generated
6.Then membrane repolarizes
7.Again depolarization and new AP
8.This cycle repeats again and again & causes self
induced rhythmical excitation of the excitable tissue

74. RHYTHMICITY IN EXICATABLE TISSUES
➢REPETITIVE,SPONT
ANEOUS AND SELF
INDUCED DISCHARGE
➢RHYTHIMICITY
OCCUR IN HEART
PACEMAKER,
PERISTALSIS OF
INTESTINE etc

75. Chapter 4 Principles of Neural
and Hormonal Communication
Human Physiology by Lauralee
Sherwood ©2010 Brooks/Cole,
Cengage Learning

76. Graded Potential vs Action
Potential

77. Principles of Action Potentials
● 1. The All or Nothing Principle:
Action Potentials occur in all or none fashion
depending on the strength of the stimulus
● 2. The Refractory Period:
Responsible for setting up limit on the frequency of
Action Potentials

78. All-or-None Principle
• If any portion of the membrane is depolarized
to threshold an AP is initiated which
will go to its maximum height.
• A triggering event stronger than one necessary
to bring the membrane to threshold does not
produce a large AP.
• However a triggering event that fails to
depolarize the membrane to threshold does
not trigger the AP at all.

79. All or none principle
●Thus an excitable membrane either respond to a
triggering event with maximal Action potential that
spread throughout the membrane in a non
decremental manner or it does not respond with an
AP at all. This is called all or non law.

80. Importance
● The importance of threshold phenomenon
is that it allows some discrimination b/w
important and unimportant stimuli .
Stimulus too weak to bring the membrane
potential to threshold do not initiate
action potentials and therefore do not
transmit the signals.

81. Refractory period
(unresponsive or stubborn)
●A new action potential cannot
occur in an excitable membrane as
long as the membrane is still
depolarized from the preceding
action potential.

82. ' Refractory Period
The absolute refractory period
a Comes immediately afler the AP;
a During this period it is impossible to excite the cell no matter how IBrge a
stimulating current is applied
a DuFing whiEh it is possible to trigger an AP, but only by applying stimuli that
are stronger thBnnomal.
Time (ms)

83. Refractory Periods
●Absolute refractory
period:
Membrane cannot produce
another AP because Na+
channels are inactivated and
no amount of excitatory
signal applied to these
channels at this point will
open the inactivation gates.
●Relative refractory period
occurs when VG K+
channels are open, making
it harder to depolarize to 7-38

84. Absolute Refractory Period
The absolute refractory period is the time from
the opening of the Na+ activation gates until the
closing of inactivation gates
When a section of membrane is generating an AP and
Na+ channels are open, the neuron cannot respond to
another stimulus

85. Relative Refractory Period
The relative refractory period is the interval following the
absolute refractory period when:
Na+ gates are closed
K+ gates are open
Repolarization is occurring
During this period, the threshold level is elevated,
allowing only strong stimuli to generate an AP (a
strong stimulus can cause more frequent AP
generation) a large suprathreshold graded potential can
start a second AP by activating Na+ channels which
have been reset

86. • Absolutely refractory period- a second AP will not occur until the first is over.
The gates on the Na+ channel have not reset.
•Relatively refractory period- a large suprathreshold graded potential can start
a second AP by activating Na+ channels which have been reset.
Refractory Periods Limit the Frequency of
APs
F8-17

87. Significance of refractory
period
●By the time the original site has recovered from its
refractory period and is capable of being
restimulated by normal current flow the AP has
been rapidly propagated in forward direction only
and is so far away that it no longer influence the
original site so ensure one way propagation of the
action potential

88. • Refractory periods limit the rate at which signals
can be transmitted down a neuron. Limit is
around 100 impulses/s.
• The greater the RP the greater the delay before a
new AP can be initiated and lower the frequency
with which a nerve cell can respond to repeated
or on going stimulation
Refractory Periods Limit the Frequency of APs

89. Refractory Periods

90. Frequency of Action Potential Firing is
Proportional to the Size of the Graded
Potential
F8-18
The amount of neurotransmitter released from the axon terminal is
proportional to the frequency of action potentials.

91. Factors Affecting Excitability of Nerve
1 Increase excitability:
-Increase Na permeability (Depolarize):
Low extracellular
LC
ow
a+
e
+
xtracellular
Increase extraIc
n
.crease
Ke
-cx
o
tn
ra
cc
e
e
n
lt
lu
ra
la
tir
on.
2 Decrease excitability (membrane stabilizers)
Decreased N
-a permeability:
High extracel,lula
H
ri
C
ga
h+
e
+
xtr
a
a
n
c
d
ellu
lo
la
cr
al anesthesia
Decrease extr
D
ae
ce
cr
lle
ua
la
sr
e-eK
xt+
rac
co
en
llc
ue
la
n
rtration.
.

92. •Membrane stabilizers :
•In addition to the factors that increases membrane
excitability still others which decreases excitability of
the membrane called membrane stabilizing factors.
•For e.g. high ECF Ca++ decreases membrane
permeability to Na+ and simultaneously reduces
excitability so Ca++ are said to be a membrane stabilizer
•Local anesthetics: they r also membrane stabilizers. E.g.
procaine and tetracaine. They act directly on the
activation gates of Na++ making it much more difficult
for these gates to open so reducing membrane
excitability.

93. Action Potential
always begin with dep.
•Graded potential
May be positive (depolarize)
Or negative (hyperpolarize)
All or none
Graded: proportional to stimulus
Strength
Reversible, returns to RMP if stimulation
Ceases before threshold is reached
Irreversible: goes to
completion once
it begin
general
Non decremental
Local: has effect for only short distance
Decremental: signal grows weaker
with distance