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Excitable tissue
Plan
• Properties of excitable tissues
• History of the study of bioelectric phenomena
• Resting potential
• Action potential of nerve cell
• Excitability change at excitation
• Propagation of an action potential in nerve
fibers
What is the tissues?
Tissues (biology, histology)
are groups of cells with
• a common origin
• a common structure
• and a similar function
Tissue
• What tissues do you know?
Tissues
Animal tissues can be grouped into
four basic types:
• Nervous tissue
• Muscle tissue
• Epithelial tissue
• Connective tissue
Excitable Tissues
• Nervous tissue
• Muscle tissue
• Glandular Epithelium
Why are they called excitable
tissues?
• Stimulus acts on tissue
• Response of Excitable tissue is excitation or
irritation
Non-excitable tissues
• Red cells
• Intestinal cells
• Fibroblasts and etc.
Why are they called non-excitable tissues?
• Response of Non-Excitable tissue is only irritation
•Excitable tissues
capable to be excited!
Excitation
• Is specific electrical response
Examples: Action Potential,
Presynaptic Potential, Postsynaptic
Potential, Receptor Potential, …
Irritation
• Is not specific electrical
response
Examples: metabolic change, taxis,
hypertrophy, hyperplasia, …
IRRITATION
Stimulus
• In physiology, a stimulus (plural stimuli) is
any external and internal influences
Classification of stimuli:
• By the nature
- the external: physical, chemical, biological
- the internal: physiologically active substances
• By force
- Subthreshold
- Threshold
- Suprathreshold
• The Threshold is the minimal stimulus capable to
cause tissue response.
THE GENERAL PROPERTIES OF EXCITABLE
TISSUES
•
1. EXCITABILITY
- is the ability of tissue to react to the stimulation with change of
physiological properties and generation of process of excitation. Excitability
of cells and tissues is a basic function of life.
2. CONDUCTIVITY
- ability to conduct impulse.
3. LABILITY
- ability to conduct certain quantity of impulses per
time.
4. CONTRACTILITY
- ability to change the size (to contract) and tension.
Physiology of Excitable Tissues
≈ Electrophysiology
Electrophysiology
• is the study of the electrical properties of
biological cells and tissues.
• It involves measurements of voltage change or
electric current on a wide variety of scales
from single ion channel proteins to whole
organs like the heart.
Animal electricity and the birth
of electrophysiology:
Luigi Aloisio Galvani
• 1737 – 1798
• was an Italian physician,
physicist and
philosopher
• Founder of
electrophysiology
• he discovered “animal
electricity”
The 1st Galvani’s experiment
In 1771, Galvani was able to cause
muscular contraction without a
source of electrostatic charge by
touching the frog’s nerve with
different metals. After further
experimenting with natural (i.e.
lightning) and artificial (i.e. friction)
electricity, he concluded that
animal tissue contained its own
innate vital force, which he termed
"animal electricity."
• A.Volta repeated L.Galvani’s experiments
and
• By 1800, Volta proved that the source of
the electricity was metals.
Alessandro Giuseppe Antonio
Anastasio Volta
• 1745 – 1827
was an Italian physicist known
for the invention of the
battery in the 1800s.
Galvani vs. Volta:
• animal electricity or chemical energy of two
different types of metal converted into
electrical energy?
• So is there an animal electricity or
not?
The 2nd Galvani’s experiment
Cut across the hip muscle of the
other leg of the frog
Place the buttock’s nerve of
the paw in the cross-section on
the leg muscle and observe the
reaction
The 2nd Galvani’s experiment
•without metal !!!
Membrane Potential
Is a transmembrane potential difference that exists
between the inner and outer surfaces of the plasma
membrane.
Em=Ein-Eout
Measurement of the membrane potential of
cells and fiber using a microelectrodes
Measurement of the membrane potential of
the nerve fiber using a microelectrode
What is the membrane potential?
Electrical potentials exist across the
membranes of virtually all cells of the body.
In addition, some cells, such as nerve and
muscle cells, are capable of generating rapidly
changing electrochemical impulses at their
membranes, and these impulses are used to
transmit signals along the nerve or muscle
membranes. In still other types of cells, such
as glandular cells, local changes in membrane
potentials also activate many of the cells’
functions.
Diffusion potentials
• A diffusion potential is the potential difference generated
across a membrane because of a concentration difference
of an ion.
• A diffusion potential can be generated only if the
membrane is permeable to the ion.
• The size of the diffusion potential depends on the size of
the concentration gradient.
• The sign of the diffusion potential depends on whether the
diffusing ion is positively or negatively charged.
• Diffusion potentials are created by the diffusion of very few
ions and, therefore, do not result in changes in
concentration of the diffusing ions.
Diffusion potential
Equilibrium Potential
The equilibrium potential is
the potential difference
that would exactly balance (oppose)
the tendency
for diffusion down
a concentration difference.
At electrochemical equilibrium,
the chemical and
electrical driving forces
that act on an ion are equal and
opposite, and no more
net diffusion of the ion occurs.
Equilibrium potential Nernst Equation
• Eion = 2.303 RT/zF log [Cion]o/[Cion]in
• Eion = equilibrium potential
• Z= charge of ion
• F= Faraday’s constant
• T= absolute temperature (0Kelvin/-273°C)
• R= gas constant
The Nernst equation is used to calculate the equilibrium
potential at a given concentration difference of a permeable ion
across a cell membrane. It tells us what potential would exactly
balance the tendency for diffusion down the concentration
gradient; in other words, at what potential would the ion be at
electrochemical equilibrium?
• RESTING MEMBRANE POTENTIAL
Resting membrane potential (RMP) - a membrane
potential of excitable cells that are at rest.
Resting Membrane Potential
• Neurons, like other cells, are more negatively
charged inside than outside
• This results in a membrane potential of about
– 70 milliVolts
• This is called the resting potential of the
neuron.
© 2016 Paul Billiet ODWS
Generation of Resting Membrane
Potential (-70mV)
• Action of ion pumps 3Na/2K ATPase that
maintain ion concentrations
• Unequal distribution of ions across
membrane
• Selective permeability, permeable to K+, not
Na+
Goldman-Hodgkin-Katz equation (G-
H-K equation, Goldman equation)
• The actual resting membrane potential (Em) for a
system involving more than one permeable ion is
calculated by the Goldman-Hodgkin-Katz equation
(G-H-K equation), which takes into account the
permeabilities and concentrations of the multiple
ions.
Em
=
RT
zF
log
PK
[K+
]o
+ PNa
[Na+
]o
+ Pcl
[Cl-
]o
PK
[K+
]i
+ PNa
[Na+
]i
+ Pcl
[Cl-
]i
Membrane Potential:
Goldman Equation
• P = permeability
– at rest: PK: PNa: PCl = 1.0 : 0.04 : 0.45
The resting membrane potential in
different cell types are approximately:
• Skeletal muscle cells: − 95 mV
• Smooth muscle cells: – 60mV
• Neurons: – 60 to –70mV
• THE ACTION POTENTIAL
The Action Potential
Is a Rapid Change in Membrane Potential
1. Depolarization
phase
2. Repolarization
phase
3. Hyperpolarization phase
Resting potential
Threshold potential
IONIC BASIS OF
ACTION POTENTIAL
ACTION POTENTIAL of NERVE CELL
Step 1: Resting membrane potential
Step 2: Some of the voltage-gated Na-channels
open and Na+ enters the cell
Step 3: Opening of more voltage-gated
Na-channels and further depolarization (rapid upstroke)
Step 4: Reaches to peak level
Step 5: Direction of electrical gradient for Na is reversed + Na-
channels rapidly enter a closed state “inactivated state” +
voltage – gated K-channels open (start of repolarization)
Step 6: Slow return of K-channels to the closed state
(hyperpolarization)
Step 7: Return to the resting membrane potential
Voltage-gated channels
How voltage-gated channels work
At the resting potential, voltage-
gated Na+ channels are closed.
Conformational changes open
voltage-gated channels when
the membrane is depolarized.
Two important types:
1.) Na+ voltage gated channels
2.) K+ voltage gated channels
Resting Potential - Both voltage gated Na+ and K+ channels are
closed.
Initial Depolarization - Some Na+ channels open. If enough Na+
channels open, then the threshold is surpassed and an action
potential is initiated.
Na+ channels open quickly. K+ channels are still closed.
PNa+ > PK+
Na+ channels self-inactivate, K+ channels are open.
PK+ >> PNa+
Hyperpolarization
Resting Potential - Both Na+ and K+ channels are closed.
An Action Potentials has 2 Refractory Periods
1. Absolute Refractory Period: During this period, the cell is
unresponsive to any further stimuli. No other action potential can
be fired at this point, regardless of the strength of the stimuli.
Explanation: Recall that the inactivation gates of the Na+ channels
are closed when the membrane potential is depolarized. They remain
closed until repolarization occurs. No action potential can occur until
the inactivation gates open.
The role of the Absolute refractory period is to ensure one-way
propagation of action potentials.
2. Relative Refractory Period: During this period, another action
potential can be produced but the strength of the stimuli must be
greater than normal to trigger an action potential.
The role of the Relative refractory period: helps to limit the
frequency of action potentials.
Refractory periods
Graded (Local) potentials
Graded (local) potentials are short-distance signals.
Distinguishing Features of Graded (Local) Potentials
and Action Potentials
Propagation of action potential
occurs by the spread of local currents to adjacent areas of membrane,
which are then depolarized to threshold and generate action potentials.
An important characteristic of action potential
propagation is that it occurs away from the point of
initiation; it cannot travel back toward its origin. As the
action potential is conducted, the area of the
membrane directly behind the action potential is still in
the absolute refractory state due to Na+ channel
inactivation, preventing retrograde conduction.
.
CONDUCTION of the ACTION POTENTIAL
• Unmyelinated nerve
axon:
– Positive charges from the
membrane ahead and behind
the action potential flow into
the area of negativity.
– By drawing off (+) charges,
this flow decreases the
polarity of the membrane
ahead of the action potential.
– This initiates a local response.
– When the threshold level is
reached, a propagated
response occurs that in turn
electronically depolarizes the
membrane in front of it.
CONDUCTION of the ACTION POTENTIAL
• Myelinated nerve
axon:
– Myelin is an effective
insulator.
– Depolarization travels
from one node of
Ranvier (where there are
gaps in the myelin
sheath, D=0.5μm) to the
next.
- This jumping of
depolarization from node to
node is called “saltatory
conduction”
– Faster than
unmyelinated axons.
Action Potential of Contractile Cardiac cells
Phase 0 - depolarization
Phase 1 - Rapid, partial, early
repolarization
Phase 2 - plateau
Phase 3 – slow repolarization
Phase 4 – resting membrane
potential (RMP)
Phase Membrane channels
PX = Permeability to ion X
+20
-20
-40
-60
-80
-100
Membranepotential(mV)
0
0 100 200 300
Time (msec)
PK and PCa
PNa
PK and PCa
PNa
Na+ channels open
Na+ channels close , K channels open
Ca2+ channels open; K+ channels open
Ca2+ channels close; K+ channels open
Resting potential
1
2
30
4 4
0
1
2
3
4
The main physiological characteristics of the AP
1. Obeys the law of "all or nothing." This means that:
• AP occurs when the stimulus, the power which is no less
than certain thresholds;
• Physical characteristics of the AP (amplitude, duration,
shape) does not depend on the power of stimulus.
2. Ability to autospread along the cell membrane without damping, i.e.
without changing their physical characteristics.
3. AP accompanied with refractory.
4 AP is no capable to summation.
QUESTIONS
1. The terms "tissue” and "excitable tissues."
2. Irritability and excitability as the main types of tissue response to stimulation.
3. Properties of excitable tissues.
Stimuli and their classification.
4. History of the study of bioelectric phenomena:
4.1. The first experience L.Galvani.
4.2. The second experiment L.Galvani without metals.
5. Methods for measuring the membrane potential.
6. Diffusion potential.
7. Equilibrium potential. Nernst equation.
8. Resting membrane potential of nerves. Origin of resting membrane potential.
9. Goldman-Hodgkin-Katz equition
10. The nerve action potential. Depolarization, repolarization, hyperpolarization, threshold stimulus,
local response.
11. Stages of the nerve action potential. Ionic bases of the action potential.
12. Propagation of an action potential in the unmyelinated nerve fibers.
13. Propagation of an action potential in myelinated nerve fibers.
14. Cardiac action potential.

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Excitable tissue Physiology

  • 2. Plan • Properties of excitable tissues • History of the study of bioelectric phenomena • Resting potential • Action potential of nerve cell • Excitability change at excitation • Propagation of an action potential in nerve fibers
  • 3. What is the tissues? Tissues (biology, histology) are groups of cells with • a common origin • a common structure • and a similar function
  • 4. Tissue • What tissues do you know?
  • 5. Tissues Animal tissues can be grouped into four basic types: • Nervous tissue • Muscle tissue • Epithelial tissue • Connective tissue
  • 6. Excitable Tissues • Nervous tissue • Muscle tissue • Glandular Epithelium
  • 7. Why are they called excitable tissues? • Stimulus acts on tissue • Response of Excitable tissue is excitation or irritation
  • 8. Non-excitable tissues • Red cells • Intestinal cells • Fibroblasts and etc. Why are they called non-excitable tissues? • Response of Non-Excitable tissue is only irritation
  • 10. Excitation • Is specific electrical response Examples: Action Potential, Presynaptic Potential, Postsynaptic Potential, Receptor Potential, …
  • 11. Irritation • Is not specific electrical response Examples: metabolic change, taxis, hypertrophy, hyperplasia, …
  • 13. Stimulus • In physiology, a stimulus (plural stimuli) is any external and internal influences
  • 14. Classification of stimuli: • By the nature - the external: physical, chemical, biological - the internal: physiologically active substances • By force - Subthreshold - Threshold - Suprathreshold • The Threshold is the minimal stimulus capable to cause tissue response.
  • 15. THE GENERAL PROPERTIES OF EXCITABLE TISSUES • 1. EXCITABILITY - is the ability of tissue to react to the stimulation with change of physiological properties and generation of process of excitation. Excitability of cells and tissues is a basic function of life. 2. CONDUCTIVITY - ability to conduct impulse. 3. LABILITY - ability to conduct certain quantity of impulses per time. 4. CONTRACTILITY - ability to change the size (to contract) and tension.
  • 16. Physiology of Excitable Tissues ≈ Electrophysiology
  • 17. Electrophysiology • is the study of the electrical properties of biological cells and tissues. • It involves measurements of voltage change or electric current on a wide variety of scales from single ion channel proteins to whole organs like the heart.
  • 18. Animal electricity and the birth of electrophysiology:
  • 19. Luigi Aloisio Galvani • 1737 – 1798 • was an Italian physician, physicist and philosopher • Founder of electrophysiology • he discovered “animal electricity”
  • 20. The 1st Galvani’s experiment In 1771, Galvani was able to cause muscular contraction without a source of electrostatic charge by touching the frog’s nerve with different metals. After further experimenting with natural (i.e. lightning) and artificial (i.e. friction) electricity, he concluded that animal tissue contained its own innate vital force, which he termed "animal electricity."
  • 21. • A.Volta repeated L.Galvani’s experiments and • By 1800, Volta proved that the source of the electricity was metals.
  • 22. Alessandro Giuseppe Antonio Anastasio Volta • 1745 – 1827 was an Italian physicist known for the invention of the battery in the 1800s.
  • 23. Galvani vs. Volta: • animal electricity or chemical energy of two different types of metal converted into electrical energy? • So is there an animal electricity or not?
  • 24. The 2nd Galvani’s experiment Cut across the hip muscle of the other leg of the frog Place the buttock’s nerve of the paw in the cross-section on the leg muscle and observe the reaction
  • 25. The 2nd Galvani’s experiment •without metal !!!
  • 26. Membrane Potential Is a transmembrane potential difference that exists between the inner and outer surfaces of the plasma membrane. Em=Ein-Eout
  • 27. Measurement of the membrane potential of cells and fiber using a microelectrodes
  • 28. Measurement of the membrane potential of the nerve fiber using a microelectrode
  • 29. What is the membrane potential?
  • 30. Electrical potentials exist across the membranes of virtually all cells of the body. In addition, some cells, such as nerve and muscle cells, are capable of generating rapidly changing electrochemical impulses at their membranes, and these impulses are used to transmit signals along the nerve or muscle membranes. In still other types of cells, such as glandular cells, local changes in membrane potentials also activate many of the cells’ functions.
  • 31. Diffusion potentials • A diffusion potential is the potential difference generated across a membrane because of a concentration difference of an ion. • A diffusion potential can be generated only if the membrane is permeable to the ion. • The size of the diffusion potential depends on the size of the concentration gradient. • The sign of the diffusion potential depends on whether the diffusing ion is positively or negatively charged. • Diffusion potentials are created by the diffusion of very few ions and, therefore, do not result in changes in concentration of the diffusing ions.
  • 33. Equilibrium Potential The equilibrium potential is the potential difference that would exactly balance (oppose) the tendency for diffusion down a concentration difference. At electrochemical equilibrium, the chemical and electrical driving forces that act on an ion are equal and opposite, and no more net diffusion of the ion occurs.
  • 34. Equilibrium potential Nernst Equation • Eion = 2.303 RT/zF log [Cion]o/[Cion]in • Eion = equilibrium potential • Z= charge of ion • F= Faraday’s constant • T= absolute temperature (0Kelvin/-273°C) • R= gas constant The Nernst equation is used to calculate the equilibrium potential at a given concentration difference of a permeable ion across a cell membrane. It tells us what potential would exactly balance the tendency for diffusion down the concentration gradient; in other words, at what potential would the ion be at electrochemical equilibrium?
  • 35. • RESTING MEMBRANE POTENTIAL
  • 36. Resting membrane potential (RMP) - a membrane potential of excitable cells that are at rest.
  • 37. Resting Membrane Potential • Neurons, like other cells, are more negatively charged inside than outside • This results in a membrane potential of about – 70 milliVolts • This is called the resting potential of the neuron. © 2016 Paul Billiet ODWS
  • 38. Generation of Resting Membrane Potential (-70mV) • Action of ion pumps 3Na/2K ATPase that maintain ion concentrations • Unequal distribution of ions across membrane • Selective permeability, permeable to K+, not Na+
  • 39. Goldman-Hodgkin-Katz equation (G- H-K equation, Goldman equation) • The actual resting membrane potential (Em) for a system involving more than one permeable ion is calculated by the Goldman-Hodgkin-Katz equation (G-H-K equation), which takes into account the permeabilities and concentrations of the multiple ions.
  • 40. Em = RT zF log PK [K+ ]o + PNa [Na+ ]o + Pcl [Cl- ]o PK [K+ ]i + PNa [Na+ ]i + Pcl [Cl- ]i Membrane Potential: Goldman Equation • P = permeability – at rest: PK: PNa: PCl = 1.0 : 0.04 : 0.45
  • 41. The resting membrane potential in different cell types are approximately: • Skeletal muscle cells: − 95 mV • Smooth muscle cells: – 60mV • Neurons: – 60 to –70mV
  • 42. • THE ACTION POTENTIAL
  • 43. The Action Potential Is a Rapid Change in Membrane Potential 1. Depolarization phase 2. Repolarization phase 3. Hyperpolarization phase Resting potential Threshold potential
  • 45. ACTION POTENTIAL of NERVE CELL Step 1: Resting membrane potential Step 2: Some of the voltage-gated Na-channels open and Na+ enters the cell Step 3: Opening of more voltage-gated Na-channels and further depolarization (rapid upstroke) Step 4: Reaches to peak level Step 5: Direction of electrical gradient for Na is reversed + Na- channels rapidly enter a closed state “inactivated state” + voltage – gated K-channels open (start of repolarization) Step 6: Slow return of K-channels to the closed state (hyperpolarization) Step 7: Return to the resting membrane potential
  • 46. Voltage-gated channels How voltage-gated channels work At the resting potential, voltage- gated Na+ channels are closed. Conformational changes open voltage-gated channels when the membrane is depolarized. Two important types: 1.) Na+ voltage gated channels 2.) K+ voltage gated channels
  • 47. Resting Potential - Both voltage gated Na+ and K+ channels are closed.
  • 48. Initial Depolarization - Some Na+ channels open. If enough Na+ channels open, then the threshold is surpassed and an action potential is initiated.
  • 49. Na+ channels open quickly. K+ channels are still closed. PNa+ > PK+
  • 50. Na+ channels self-inactivate, K+ channels are open. PK+ >> PNa+
  • 52. Resting Potential - Both Na+ and K+ channels are closed.
  • 53. An Action Potentials has 2 Refractory Periods 1. Absolute Refractory Period: During this period, the cell is unresponsive to any further stimuli. No other action potential can be fired at this point, regardless of the strength of the stimuli. Explanation: Recall that the inactivation gates of the Na+ channels are closed when the membrane potential is depolarized. They remain closed until repolarization occurs. No action potential can occur until the inactivation gates open. The role of the Absolute refractory period is to ensure one-way propagation of action potentials. 2. Relative Refractory Period: During this period, another action potential can be produced but the strength of the stimuli must be greater than normal to trigger an action potential. The role of the Relative refractory period: helps to limit the frequency of action potentials.
  • 55. Graded (Local) potentials Graded (local) potentials are short-distance signals.
  • 56. Distinguishing Features of Graded (Local) Potentials and Action Potentials
  • 57. Propagation of action potential occurs by the spread of local currents to adjacent areas of membrane, which are then depolarized to threshold and generate action potentials. An important characteristic of action potential propagation is that it occurs away from the point of initiation; it cannot travel back toward its origin. As the action potential is conducted, the area of the membrane directly behind the action potential is still in the absolute refractory state due to Na+ channel inactivation, preventing retrograde conduction. .
  • 58. CONDUCTION of the ACTION POTENTIAL • Unmyelinated nerve axon: – Positive charges from the membrane ahead and behind the action potential flow into the area of negativity. – By drawing off (+) charges, this flow decreases the polarity of the membrane ahead of the action potential. – This initiates a local response. – When the threshold level is reached, a propagated response occurs that in turn electronically depolarizes the membrane in front of it.
  • 59. CONDUCTION of the ACTION POTENTIAL • Myelinated nerve axon: – Myelin is an effective insulator. – Depolarization travels from one node of Ranvier (where there are gaps in the myelin sheath, D=0.5μm) to the next. - This jumping of depolarization from node to node is called “saltatory conduction” – Faster than unmyelinated axons.
  • 60. Action Potential of Contractile Cardiac cells Phase 0 - depolarization Phase 1 - Rapid, partial, early repolarization Phase 2 - plateau Phase 3 – slow repolarization Phase 4 – resting membrane potential (RMP) Phase Membrane channels PX = Permeability to ion X +20 -20 -40 -60 -80 -100 Membranepotential(mV) 0 0 100 200 300 Time (msec) PK and PCa PNa PK and PCa PNa Na+ channels open Na+ channels close , K channels open Ca2+ channels open; K+ channels open Ca2+ channels close; K+ channels open Resting potential 1 2 30 4 4 0 1 2 3 4
  • 61. The main physiological characteristics of the AP 1. Obeys the law of "all or nothing." This means that: • AP occurs when the stimulus, the power which is no less than certain thresholds; • Physical characteristics of the AP (amplitude, duration, shape) does not depend on the power of stimulus. 2. Ability to autospread along the cell membrane without damping, i.e. without changing their physical characteristics. 3. AP accompanied with refractory. 4 AP is no capable to summation.
  • 62. QUESTIONS 1. The terms "tissue” and "excitable tissues." 2. Irritability and excitability as the main types of tissue response to stimulation. 3. Properties of excitable tissues. Stimuli and their classification. 4. History of the study of bioelectric phenomena: 4.1. The first experience L.Galvani. 4.2. The second experiment L.Galvani without metals. 5. Methods for measuring the membrane potential. 6. Diffusion potential. 7. Equilibrium potential. Nernst equation. 8. Resting membrane potential of nerves. Origin of resting membrane potential. 9. Goldman-Hodgkin-Katz equition 10. The nerve action potential. Depolarization, repolarization, hyperpolarization, threshold stimulus, local response. 11. Stages of the nerve action potential. Ionic bases of the action potential. 12. Propagation of an action potential in the unmyelinated nerve fibers. 13. Propagation of an action potential in myelinated nerve fibers. 14. Cardiac action potential.