3. Objectives of the lecture:
By the end of the lecture the student should be able to:
• Understand meaning of excitability
• Differentiate between excitable & non-excitable tissues
• Illustrate factors determining the effectiveness of the stimulus
• Discuss strength duration curve
• Mention properties of nerves
4. Excitability
** The response is in the form of change in membrane potential
(generation of nerve impulse = action potential= electrical signal)
** The stimulus is the change in the environment of the living tissue
which may be: electrical, chemical, mechanical or thermal.
The electrical stimuli are commonly used in the form of:
Galvanic current: direct e.g. from a battery
Faradic current: alternative.
It is the ability of the living tissue to respond to an adequate stimulus.
** Some cells are excitable e.g. nerve cell & muscle cell, while others are
non-excitable.
5. Factors that determine the effectiveness of the stimulus:
1- Intensity (strength) of the stimulus:
Threshold stimulus: is the minimal intensity which can
produce nerve impulse in the nerve fiber.
Sub-threshold stimulus no impulse but local response
Supra-threshold stimulus the same impulse of the
threshold stimulus.
6. All or none law:
• A threshold stimulus produces maximal action potential (AP) and increasing
intensity of stimulus above threshold value produces no further increase in
amplitude of AP, and if we use a subthreshold stimulus no impulse will be developed
at all
• i.e. AP occurs with constant amplitude and form regardless of the strength of the
stimulus
It is obeyed in:
1. Single nerve fiber
2. Single muscle fiber
3. Cardiac muscle
N.B.: The nerve fiber obeys all or none law.
The nerve trunk gives greater response as it
is formed of many nerve fibers and each
fiber has its threshold stimulus.
7. 2- Rate of rise of intensity of the stimulus:
If a sub-threshold stimulus is applied to the nerve fiber and intensity
increased slowly the nerve fiber accommodates itself to the passage
of the current and no response will occur.
However, If the intensity is increased very rapidly, no
accommodation and a response will occur.
8. 3- Duration of the stimulus:
Strength-duration curve:
There is a relationship between the intensity of
the stimulus and the time of its application to
the nerve to give a response,
Within limits, the stronger the stimulus, the
shorter its duration.
10. • Rheobase: is the minimal strength of electric current needed to give
a response.
From the curve:
• Utilization time: is the time required for Rheobase to give a response.
• Chronaxie: is the time required for double rheobase to give a response.
** It is a measure of tissue excitability
** Chronaxie is inversely proportional to excitability as the shorter the
chronaxie, the greater the excitability.
• Minimal time: it is the time below which no excitation occurs whatever the
strength of the stimulus.
11.
12. Clinical Significance of the Strength-Duration Curve:
• It ascertains the excitability of the nerve and thus, can detect the
magnitude of nerve damage.
• It can show recovery over a period of time.
• It is a valuable diagnostic and prognostic tool.
• It is usually performed after 3 weeks of nerve injury
13.
14. Properties of nerves
1- Excitability.
2- Conductivity.
3- All or none law.
4- Accommodation:
• The nerve adapts itself to the stimulating current.
• Constant current produces a response on make and break of current & when strength is
increased suddenly.
5- Infatiguability: the nerve is not fatigued by repeated stimulations.
16. • Define resting membrane potential (RMP)
• Mention normal range of RMP
• Illustrate evidence of resting membrane potential
• Differentiate between different types of ionic channels
• Discuss causes of resting membrane potential
• Explain importance of Na+/K+ pump
Objectivesofthelecture:
Bytheendofthelecturethestudentshouldbeableto:
17. The resting membrane potential (RMP):
Definition:
• It is the potential difference between inside and outside the cell
membrane with inside relatively negative to outside.
• RMP exists in all excitable and non excitable cells of the body.
• It ranges from – 8 to –100 mv.
• e.g. :
-70 mv in medium sized nerve fibers
- 90 mv in large nerve fibers
- 90 mv in skeletal muscle fibers
19. • If 2 electrodes connected to a galvanometer are put on the outer
surface of the cell membrane or on the inner surface of the cell
membrane, there is no deflection on the galvanometer
• (i.e. there is no potential difference).
• But if one electrode is put on outside and the other inside the cell
membrane there is deflection in the galvanometer, which indicates
presence of potential difference.
Evidence:
22. Causes of RMP:
It is due to unequal distribution of ions across the cell membrane
[outside: Na+(142mEq./L), Cl-(103mEq./L), HCO3
-(28mEq./L) and
inside: K+(140mEq./L)& protein-(40mEq./L)) with more cations
outside and more anions inside.
[I] Selective permeability of the cell membrane
This unequal distribution is caused by three factors:
[II] Na+ / K+ pump
[III] The membrane is impermeable to the intracellular protein anions
23. [I] Selective permeability of the cell membrane:
• The cell membrane is semi-permeable and has pores
(channels).
• We have two types of ion channels :
• 1- Open channels (leakage)
• 2- Gated channels
24. a- Leakage channels (passive)
They are characterized by:
-They are opened all time, not gated, tube shaped.
-Watery pathway through protein molecule.
-They are highly selective and this selectivity depends on diameter of channel,
shape of channel and charges inside the channel.
- e.g. Na+ channel has negative charges which pull Na+ to inside the cell.
However, K+ channels are not charged.
27. They have gates :
**Na+ channels have outer activation and inner inactivation gates .
** K+ channels have one inner gate.
These gates may be opened or closed by:
1- Change in membrane potential (Voltage gated channels)
2- Binding with certain chemical substances (ligand gated channels).
B- Gated channels (active)
N.B. During rest the movement of ions is through the leakage channels but during
stimulation and action potential it occurs via the gated ones.
31. • i.e. K+ ions diffuse from inside to outside according its concentration gradient
adding more positive charges to outside
Membrane permeability:
- As regard to K+: The cell membrane is highly permeable to K+.
• if we suppose that the membrane is permeable only to K+. The K+ ions
diffuse from inside to outside according its concentration gradient till the
+ve charges outside the membrane repel more K+ diffusion (electrical
gradient).
• An equilibrium is reached at which K+ outflux according to its concentration
gradient equal K+ influx down its electrical gradient (the equilibrium occurs
at membrane potential = - 94 millivolt.).
32. Membrane permeability:
- As regard to Na+:
• Na+ tends to diffuse into the cell according to its concentration and
electrical gradient but this is limited due to low permeability of membrane
to Na+ accumulation of positive charges outside the cell.
• Na+ diffuse into the cell according to its concentration gradient until it is
balanced by Na+ efflux according to electrical gradient, at equilibrium the
membrane potential = +61 millivolt.
• K+ permeability is about 100 times greater than Na+ permeability.
33. - Nernest equation: used to determine the equilibrium potential of each ion.
Electromotive force (EMF) = 61 log (concentration inside/conc. outside the
membrane).
e.g for Na+ EMF = -61 log (15/150) = +61 millivolt.
for K+ EMF = -61 log (150/5) = -94 millivolt.
-According to the degree of the permeability of the membrane to Na+ and K+ the
potential will be determined.
- Goldman equation: is used to determine the equilibrium potential of all ions ,
which is about –86 millivolt (near to the equilibrium potential of K+ indicating that
K+ permeability is the main force responsible for the resting membrane potential.
34. [II] Na+ - K+ pump:
- At rest, some Na+ can enter inside the nerve fiber
- Also during action potential large number of Na+
enter the cell
- K+ efflux occurs also during rest and action potential.
- So, the Na+ pump is required to return Na+ outside
(against conc. and electrical gradient) and K+ pump is
required to return K+ inside the cell against the
concentration gradient.
36. Na+-K+ pump needs:
• The energy source for this pump is (ATP)
• ATPase enzyme is needed for liberation of energy from ATP.
• Large carrier protein present in the cell wall.
Its internal surface has 3 receptors for Na+ and ATPase
The external surface has two receptors for K+.
• When activated by energy from splitting of ATP; it pumps
3 Na+ to outside and 2K+ to inside the cell.
37. Importance of the Na+-K+ pump:
1- Maintenance of Na+ (extra cellular) and K+
(intracellular).
2- It is an electrogenic pump as it causes RMP
to be more negative inside (- 4 mvolt), (2K+
influx against 3 Na+ outflux).
3- Control of cell volume as if Na+ remains inside
the cell, water enters by osmosis and the cell
swells.
38. Selective permeability Na+/K+ pump
• Initiation of the RMP
(-86 mvolt).
• Passive process.
• K+ is mainly responsible
• Maintenance of RMP by
- 4mvolt.
• Active process
• Na+ and K+ are responsible
39. [III] The membrane is impermeable to the intracellular anions
)proteins, phosphate ….) (due to large molecular weight)
• more negative charges inside the cell
• and according to, Donnan effect, this protein regulates diffusion
of other anions and cations until reach equilibrium
• Donnan’s equilibrium :
Cl- x K+ (inside) = Cl- x K+ (outside)
40. Net value of RMP:
(i) K+ diffusion potential = − 94 mV .
(ii) Na+ diffusion potential = +8 mV .
(iii) Na+/K+ Pump’s contribution = − 4mV .
Net RMP = − 90 mV
42. Objectivesofthelecture:
Bytheendofthelecturethestudentshouldbeableto:
• Define action potential (AP)
• Mention importance of AP
• Understand the concept of recording of AP using Cathode Ray Oscilloscopes (CRO).
• Clarify phases of action potential
• Explain ionic bases of action potential
• Compare between different types of AP
• Mention properties of action potential
• Describe excitability changes during AP
• Enumerate factors affecting excitability
• Understand mechanism of nerve impulse conduction
• Illustrate factors affecting conduction velocity.
43. (B) Action potential :
-Definition:
It is a transient change in the resting membrane
potential as a result of application of threshold stimulus.
44.
45. Importance of AP:
• Nerve impulse is required for sensation, movement, hearing , glandular
secretion, etc..
• It is the main language of the nervous system
• Any motor order or sensory information is conducted through nervous
system in the form of action potential (= nerve impulse = electrical signal)
46. Recording of action potential:
Device: Cathode Ray Oscilloscopes (CRO) using microelectrodes.
Concept:
An oscilloscope is a device which allows the amplitude of electrical signals (current,
voltage, power ) to be display in relation to time.
The basic components
The cathode ray tube itself is composed of an electron gun and a fluorescent
screen against which electrons are fired.
Where the electrons hit the screen surface, the fluorescent material glows.
If the electron beam is moved across the screen, the spot of glowing light
also moves and draws a fluorescent line on the screen.
48. Oscilloscope Working Principle
The signal is to be viewed on the screen being applied across the Y-plates of CRT. To
see the waveform of the input signal, it is essential to spread it horizontally from left
to right, which is done by applying a saw-tooth voltage wave to X-plates. Under these
conditions, the electron beam would move uniformly thereby graphing vertical
vibrations of input signal with respect to time.
50. Application of an adequate electric stimulus of the
nerve fiber is followed by:
1) Stimulus artifact:
- It is caused by current leakage from stimulating
electrode to the recording electrode
- (It indicates beginning of stimulus).
2) Latent period:
- It represents the time that the nerve impulse takes
to travel from the stimulating to recording electrode.
- It indicates the rate of conduction in the axon
- (speed of conduction = distance between the 2
electrodes/latent period).
51. 3- Spike potential (depolarization & repolarization):
(a) Depolarization (ascending limb)
-At first slow depolarization of 15 mv (RMP changed from –70 to –55 mv) at
this point (firing level) the depolarization occurs rapidly till the potential zero
and then reversal of polarity (overshoot) till +35 mvolt.
-So the magnitude of the depolarization phase equals 105 mv (from –70 to
+35 mv).
-Cause : Excessive Na+ influx by activation of Na+ gates.
52. The ionic changes during depolarization phase:
Stimulation of the nerve cell causes opening of some outer Na+ gates
Na+ influx and depolarization occurs more opening of gates and
more depolarization in a +ve feedback till depolarization reaches the
firing level (Na+ permeability reaches maximum level)
then depolarization occurs rapidly till its peak and then the inner Na+
inactivation gates close.
53.
54. (b) Repolarization (descending limb):
-It is the return
of the membrane
potential to the
resting state
(from +35 to –70
mv).
-It occurs in 3 steps:
55. 1- Rapid repolarization:
- During which the membrane
restores 70% of its resting
condition (depolarization
& rapid repolarization takes
2 millisecond).
Cause (ionic changes):
- Inactivation of Na+ gates ( Na+ permeability to inside = Na+ influx stops )
- Activation of K+ gates ( K+ permeability to outside = K+ efflux starts).
56. 2- Negative after potential (after depolarization):
- After 70% of repolarization,
the rate of repolarization
becomes slow for 4
milliseconds).
Cause:
- Decrease in K+ gradient slow K+ efflux slow repolarization.
57. 3- Positive after potential (after hyperpolarization):
- After reaching the RMP, there is
an overshoot of about 1-2 mv.
hyperpolarized then return to
normal RMP at 40 m.sec.
Cause:
- Delay of K+ channels closure more K+ efflux hyperpolarization
- Then Na+/ K+ pump restores the RMP.
58.
59. *Ionic basis of action potential:
-Na+ channels have 2 gates, outer (activation gate) and inner
(inactivation gate).
-During rest: the activation gate is closed & inactivation gate is opened
no Na+ influx.
-During depolarization: the activation gate opened and Na+
permeability reach maximum till the potential of +35 mvolt. then
the inactivation gate closed.
-Then the resting condition return when the RMP return to
normal.
The changes in the membrane potential during phases of action potential
depends on presence of the voltage gated channels:
(1) Voltage-gated Na+ channel:
60. (2) Voltage-gated K+ channel:
- K+ channel has a single gate which located inside
the membrane.
- During rest: the gate is closed.
- During depolarization slow opening of K+
channel which coincides to closure of Na+ gates at
the end of depolarization repolarization.
61.
62. From the above, stimulation of the nerve is followed by:
1- Opening of outer Na+ gates activation of Na+channels
2- Closure of inner Na+ gates inactivation of Na+channels
3- Opening of K+ gates activation of K+channels
64. *Properties of Action potential:
1-It needs threshold stimulus.
2-Propagates in both direction.
3-Obeys all or none law.
4-It has constant duration.
5-Caused by ionic changes.
65. [II] Excitability changes during action potential:
At first, there is increase in excitability till the firing
level then the following changes occur:
1- Absolute refractory period:
• No response to any stimulus (loss of excitability).
• Coincides with depolarization from the firing level till the
first 1/3 of repolarization.
• During this period Na+ gates are inactivated and not open again till
return of membrane potential to the resting state.
67. 2- Relative refractory period:
• Stronger stimulus is needed to produce response
• Low excitability
• Coincides with lower part of repolarization.
• During it Na+ gates are partially returned to resting state and
can be opened, but also, K+ channels are open causing
depolarization to be difficult.
68. 3- Supernormal phase:
• Weak stimulus can produce response
• (high excitability).
• Coincides with the negative after potential.
• During it the membrane is partially depolarized and has
low threshold for firing level.
69. 4- Subnormal phase:
• Stronger stimulus is needed to produce response
• (low excitability).
• Coincides with the positive after potential.
• During it the membrane is hyperpolarized with increase
threshold for firing level and difficult stimulation.
70. Factors Affecting Excitability of The Nerve:
(B)Factors that decrease excitability
(membrane stabilizers):
(A)Factors that increase excitability:
1- Cooling
1- Warming.
2- Ca++ concentration in extracellular fluid
2- Ca++concentration in extracellular fluid
as in tetany.
3- K+ extracellular as it leads to increased
K+ efflux and state of hyperpolarization.
3-K+ extracellular as it leads to decreased
K+ efflux and state of partial depolarization.
4- Na+ extracellular
4- Na+ extracellular
5- Acidosis.
5- Alkalosis.
71. (B)Factors that decrease excitability
(membrane stabilizers):
(A)Factors that increase excitability:
-Mechanical pressure.
-Decrease blood supply to the nerve (ischemia)
-Hypoxia (Decrease O2 supply to the nerve)
Factors Affecting Excitability of The Nerve:
72. *Familial periodic paralysis in which there is hereditary decrease in
extracellular K+ excitability & contraction of the muscle muscle
relaxation and ECG changes.
*Tetany : neuromuscular excitability by extracellular Ca++.
73. 1-Monophasic action potential:
• It is the recording of potential
difference between inside and
outside the nerve fiber membrane
at one point after stimulation
Types of action potential:
74. 2- Biphasic action potential
• It is the potential changes between 2 areas (A & B) on the outer
surface of the nerve fiber membrane by using 2 microelectrodes
connected to galvanometer or Cathode Ray Oscilloscope (CRO).
• The stimulus is applied near the A point.
• It consists of the following phases:
1. At first, there is no potential difference between A & B because both are +ve.
2. When the depolarization wave reaches (A) it becomes (-ve) relative to B (+ve) and deflection
is recorded.
3. When the depolarization wave leaves (A) it repolarizes to (+ve) so no pot. difference between
A & B. (isoelectric)
4. When the depolarization wave reach (B) it becomes (-ve) relative to (A) deflection in the
opposite direction.
5. When the depolarization wave leaves (B) it repolarizes and A & B becomes again isoelectric
(both +ve) no deflection.
76. 3-Compound action potential
If a mixed nerve is stimulated
multiple peaks of action potentials will
develop, as the threshold of stimulus,
distance from electrode and speed of
conduction vary from one fiber to
another according to its thickness, till the
maximal stimuli is reached, all nerve
fibers are excited giving maximal
response.
77. 1-Subthreshold stimulus no response.
2-Threshold stimulus potential changes of some more excitable fibers.
3-Suprathreshold stimulus more fibers are excited with more response.
4-Maximal stimuli all fibers are excited and give maximal response.
5-Supramaximal stimuli the same maximal response.
Compound action potential
82. -
- At the site of stimulation the membrane is depolarized (-ve outside).
Then a local circuit of current flow occurs between the depolarized area
and surrounding (resting) areas.
- In the outer surface +ve charges migrate from the adjacent point to the
point of depolarization.
- In the inner surface +ve charges migrate from the point of depolarization
to the adjacent (resting) point.
(1) In unmyelinated nerve fibers:
83. • The point of stimulation begins to repolarize.
• The surrounding sites begin to depolarize partially till
they reach the firing level action potential occurs, and
conduction occurs along the nerve fiber.
• The speed of propagation is directly proportional to the
diameter of the nerve fiber
The results are:
84. • The same mechanism as in unmyelinated but the impulse jumps from one
node of Ranvier to the other because the myelin is insulator for current.
• So, it is called jumping or saltatory conduction or node to node conduction
(2) In myelinated nerve fibers:
85. • The rate of conduction in myelinated nerve is 50 to
100 times faster than in unmyelinated.
• It occurs with less energy consumption for Na +/K+
pump (more economic).
Saltatory Conduction Is Characterized By:
86. Orthodromic conduction:
In normal direction from cell body along the axon till its end then to next
neuron.
Antidromic conduction:
Conduction in opposite direction to the usual pathway.
87. Factors affecting conductivity in the nerve.
1- Diameter of the nerve fibre :
• diameter conduction
• The nerve fibers are classified into 3 types
according its diameter:
88. C Fibres
B Fibres
A Fibres
Less than 1
up to 5
up to 20
- Diameter
0.5 – 2 m/sec
5 – 15 m/sec
20 – 120 m/sec
-Speed of
conduction
2 msec.
1 msec.
0.5 msec.
-Duration of A.P.
Local anaesthesia
hypoxia
Mechanical
pressure
-Susceptible to
Non-myelinated
Myelinated
Myelinated (alpha,
beta, gamma &
delta)
-Myelin sheath
Post ganglionic
Preganglionic
Somatic nerve
fibres
- e.g.
89. 2) Myelination:
as myelinated axon is 50-100 times faster than unmyelinated one.
3) Local anasthetics
conduction with more effect on C fibers.
4) Mechanical pressure
conduction (with more effect on A-fibres)
5) Hypoxia conduction (with more effect on B fibres).
90. Action Potential
Local Response
-Threshold or suprathreshold
-Propagated
-Cannot be graded
-Obeys all or non law
-Cannot be summated
-It has absolute refractory period
-Variable
1-Due to subthreshold stimulus
2-Localized
3-Can be graded
4-Does not obey all or none law
5-Can be summated
6-No absolute refractory period
7-The excitability increased
Effect of subthreshold stimulus: Local Response
Definition: Local non propagated depolarization at site of stimulation
