PHYSIOLOGY OF

EXCITABLE TISSUE
The fluid mosaic model of membrane
structure
 Functions of membrane proteins
 Transport
 Structure
 Receptors
 Enzymes
 Antigens
 BIOMEDICAL IMPORTANCE
 Gross alterations of membrane structure can affect water
balance and ion flux and therefore every process within the
cell. Specific deficiencies or alterations of certain
membrane components lead to a variety of diseases.

 Examples include the lysosomal absence of acid maltase,

causing type II glycogen storage disease; the lack of an
iodide transporter, causing congenital goiter; and defective
endocytosis of low-density lipoproteins, resulting in
accelerated hypercholesterolemia and coronary artery
disease
 Sponsored
Medical Lecture Notes – All Subjects

USMLE Exam (America) – Practice

 Transport Across Membranes
 1. Macrotransport

 2. Microtransport
 Macrotransport

 1. Endocytosis

 A. Phagocytosis
 B. Pinocytosis

 2. Exocytosis
 Microtransport

 1. Passive

 2. Active
 Passive transport
 1. Diffusion (simple & facilitated)

 2. Osmosis

 3. Filtration
 Simple diffusion
 Movement of molecules in response to a
concentration gradient.

 It doesn’t need energy

 Facilitated diffusion
 It doesn’t need energy too, but needs
special carries
 Movable
 Immovable
Mechanism of Facilitated diffusion
 Active transport
 Goes against concentration gradient and
requires energy.

 1. Primary

 2. Secondary
 Primary active transport
 This is transportation of the ions with the
help of special enzymatic transport systems
(ATP-ases)

 E.g. Na / K – pump
Extracellular Intracellular fluid
fluid
E
x
t
r
a
c
e
l
l
u
l
a
r

s
p
a
c
e
 m m
m

1 2
h 3
h h

The number of opened channels regulates

membrane permeability
The work of voltage gated Na+–channel.

h – internal
inactivational gates
(slow, can’t be
stimulated)

m – external
activational gates
(fast, can be
stimulated)
 State of rest for the cell
 Membrane is permeable for potassium
 Potassium leaves the cell & polarizes the
membrane
 Membrane is slightly permeable for sodium,
which enters the cell & decreases the charge
 Membrane charge at the state of rest is -90 to -
50mV
 «Electrical gradient»
 Is an electric force created by trans-membrane
charge
 Potassium efflux increases electrical gradient
 As the result concentration gradient becomes
equal to electrical
 Equilibrium potential
 Equilibrium state – is such an electrical
charge on the membrane which completely
balances the concentrational gradient for a
certain ion & the current for this ion is 0.
 Potassium equlibrium potential =
-97,5 mV (Ек+ = -97,5 mV )
 Mechanisms maintaining ionic
asymmetry
 Electrical charge on the membrane – enables
potassium influx & inhibits its efflux

 Sodium-potassium pump – active cross

membrane transport against concentration
gradient
 SODIUM-POTASSIUM PUMP
Active transport of potassium & sodium ions
against concentration gradients with ATP
expenditure
3Na+

2K+
ATP
 SODIUM-POTASSIUM PUMP
FUNCTIONS
 Active transport of ions maintains
concentration gradients

 Electrogenic effect (adds up to 10% to the

value of resting potential )
 depolarization
 Occurs at the opening of sodium channels
 Sodium enters the cell:
 decreases negative charge on the inner surface
of the membrane
 Decreases electrical gradient
 Level of depolarization depends on the
number of opened sodium channels
 CRITICAL LEVEL OF
DEPOLARIZATION ЕCR
 Charge on the membrane which opens max
amount of sodium channels
 This number of opened channels is critical for
further development of action potential
 «evelange» sodium influx
 sodium influx is 20 times more than potassium
efflux
 Regenerative depolarization starts
 Threshold of depolarization
 Difference between resting potential (Е0)
&critical level of depolarisation (Еcr)
Δ V= Е0 - Еcr
 Is in inverse proportion to excitability – the
lower is the threshold, the higher is
excitability of the membrane
Subthreshold depolarization or local
response (LR)
 Active local short lasting reverse membrane
depolarization in response to sub-threshold
stimuli
 Small amount of sodium channels opens and
regenerative depolarization doesn’t start
 «ALL OR NONE» law
 Sub-threshold stimuli cause local
depolarization («none»)
 Threshold & supra-threshold stimuli cause
maximum response in the form of AP («all»)
 LR properties
1. Doesn’t obey «all or none» law, i.e.
2. LR amplitude depends on the force of the
stimulus (the greater is the stimulus the higher
is the LR magnitude)
3. Doesn’t spread to vast distances, spreads with
the decrease of its magnitude
4. LRs can be summed up in time and space
5. If the sum reaches critical depolarization level
they can be transformed into AP
 Regenerative depolarization
Membrane
Stimulatio
Stimulus
STIMULU depolarization
n S

Sodium Increased
Sodium
influx permeability

Self supporting depolarization, which doesn’t

require further stimulation.
 ACTION POTENTIAL (AP)
 Action potential (AP) is a difference of
potentials between depolarized and non-
depolarized parts of the membrane,
 which occurs as the result of quick
membrane depolarization
 with the following restoration of membrane
potential.
 mV
+30

2 3

Еcr
1 4

Е0
-80 5
 AP phases
1. Slow depolarization
2. Quick depolarization
3. Quick repolarization
4. Slow repolarization
5. After potential hyperpolarization
 Action potential
Ionic currents of sodium & potassium
+30

Екр

Е0

Na+

К+
 AP development conditions
 Depolarization should reach critical level

 Sodium influx should be 20 times more than

potassium efflux

 Regenerative depolarization should start

 Excitability changes during AP
development
 Excitability is in inverse proportion to
depolarization threshold
Δ V= Е0 - Еcr

 ΔV excitability

 ΔV excitability
+30

Еcr

Е0
1 4

5
3

2
 +30

Екр

Е0
1 4
100%

5
3

2
0
 Stages of excitability (related to AP
phases)
1. Supernormal period
2. Absolute refractory period – no
excitability
3. Relative refractory period (excitation only
after super-threshold stimulation)
4. Supernormal period
5. Subnormal period
 AP parameters
 Magnitude - AP magnitude is 120-130μV

 Duration - average is 3-5 msec (in different

tissues it may be from 0,01 msec to 0,3 sec)

 Shape - plato-like or peak-like

 Are constant for the cells of each tissue

LAWS OF IRRITATION
 Irritation
 Is a process of cell stimulation

 The effect of irritation depends on quantity &

quality characteristics of the stimulus

 as well as on the properties of the cell itself

 Types of irritation (stimuli)
 Mechanical
 Temperature
 Chemical
 Biological
 Electrical
 Advantages of electrical stimuli
1. Constructs biological processes
(biopotentials)
2. Easy to change in:
 Force
 Time
 Steepness of force growth
 LAWS OF IRRITATION
are the rules which describe requirements for the
stimulus to cause excitation. They are :

• law of polarity
• law of force
• law of time (duration of stimulation )
• law of steepness (time of force growth)
 Law of polarity
On extracellular application of rectangular
electrical impulses excitation occurs

on make (closed circuit) under cathode, on

break (opened circuit) under anode
 CLOSED CIRCUIT

-+ -
+ CATHODE + - +
ANODE -

+
-
 OPENED CIRCUIT

-+ -
+ CATHODE + -
ANODE
 LAWS OF IRRITATION
 LAWS OF IRRITATION is a complex of laws which
point out the requirements for a stimulus able to cause AP.
 Polarity law – on the extracellular application of constant

rectangular current excitation occurs under cathode on

closed circuit and under anode on the opened circuit.
 Law of force – to cause AP stimulus should have certain
force not lower than the threshold one.
 Law of time – to cause AP stimulus should be applied during
the time not shorter than the threshold one.
 Law of steepness – to cause AP stimulus should have certain
steepness not lower than the threshold one.
 А – law of
force
 B – law of
steepness.
 C – law of
time
 I - MP
changes.
 II –
stimulus
 1 and 2 –
subthreshol
d stimuli,
 3 –threshold
stimulus
 FORCE-TIME CURVE
R – reobase – minimum force
that causes AP force
UT – utilization time – minimum
time of 1 reobase application
to cause AP.
Chr – chonaxy - minimum
time of 2 reobase application
to cause AP.
2R
R

Chr UT time
 Accomodation
 Is tissue ability to get adjusted to long lasting
& low steepness stimulation.
 Critical level of depolarization decreases to
zero
 Sodium channels don’t open simulteneously &
sodium influx is compensated by potassium
efflux.
 There can be no regenerative depolarization &
AP doesn’t occur
ACCOMODATION