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‫بسم هللا الرحمن الرحيم‬

Dr. Othman Al-Shboul


Department of Physiology
College of Medicine
JUST

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“hydraulic mechanism”: muscles contract because
fluid flowing into them from hollow nerves!!!

Galen
(129-210 AD)

https://nba.uth.tmc.edu/
neuroscience/m/s1/chapt
er01-hydroneuron.html 3
“animal spirits” flowed from the brain through nerves
and then to muscles to produce movements!!!

René Descartes
(1596 – 1650)

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nerve and muscle could be activated by charged
electrodes and suggested that the nervous system
functions via “electrical signaling”

Luigi Galvani
(1794)

https://nba.uth.tmc.edu/n
euroscience/m/s1/chapter0
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1-galvani.html
development of modern electronic amplifiers and
recording devices that allowed the electrical signals to
be recorded

(1930s)

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recording electrical signals in optic nerve surface
in the horseshoe crab Limulus

H.K. Hartline
(1956)

https://nba.uth.tmc.edu/neur
oscience/m/s1/images/html5/S aquariumofpacific.org

1.1.2-F1.1/1.1.html 7
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+ -
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+ Repulsion +
Push Work

+ Attraction
Pull Work
-
10
So, charged particles have the ability to do work

i.e., able to make each other or other objects move

+ -
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v
Membrane Potential(Vm) voltmeter

+ -
 Separation of charges across + -

Membrane
the membrane
+ -
+ -
 Potential is measured in units of volts
(or millivolt (mV)) + -
+ -
+ - 12
Two factors are important for the
generation of the membrane potential

Asymmetric distribution of Selective permeability of the


charges across the membrane membrane

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Asymmetric distribution of
charges across the membrane

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+ & - charges are equally balanced on each
side of the membrane
Membrane

Electroneutrality Electroneutrality

Number of + = Number of - Number of + = Number of -

Membrane has NO potential 15


+ & - charges are unequally separated across
the membrane

Excess Positivity Excess Negativity

Membrane has potential 16


↑ number of charges separated → ↑ potential
< <
Magnitude of the
potential depends
on the degree of
separation of the
opposite charges

Excess Excess
positivity Negativity
6 6 17
Selective permeability of the
membrane

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What is Diffusion ???
20 0

Green-colored
uncharged
molecules
Concentration
20 Gradient
0
Concentration
10 Gradient
10

NO Concentration
Gradient
0

- +

NO
membrane
20 Potential 0

- -
- + -
+ +
+ - +
-
+ - + +
+ -
- +
- + -
+ -
+
- + +
- + - - -
+ +
- + - + -

No openings in the membrane


Concentration
20 Gradient 0

- -
+
- + - Non-
+ +
- - + selective
+ - +
+ + - openings
- +
- + -
+ -
+
- + +
- + - - -
+ +
- + - + -
0

- +

NO
membrane
10 Potential 10

- -
- + -
+ +
+ - +
-
+ - + +
+
- Electroneutrality +
Electroneutrality
- -
- + -
+ +
- + +
- + - - -
+ +
- + - + -

NO Concentration Gradient
Channels are closed; no movement of +

Channel
specific for +
20 0

- -
- + -
+ +
+ - +
-
+ - + +
+ -
- +
- + -
+ -
+
- + +
- + - - -
+ +
- + - + -
Channels open

Concentration
Gradient
20 0

- -
- + -
+ +
+ - +
-
+ - + +
+ -
- +
- + -
+ -
+
- + +
- + - - -
+ +
- + - + -
In the beginning; few charges move

Concentration
Gradient
Force
develops in
- -
+
the opposite
- -
+ + direction
+ - +
- +
+ Repulsion by +
+ + - - +
- +
- - +
+ - Attraction by -
+
- +
- + - - -
+ +
- + - + -

Electrical Gradient
With movement of more charges

Concentration
Gradient ↓

- -
- + -
+ +
+ - +
- + +
+ - +
+ - +
- +
- - +
- +
- +
- + - - -
+ +
- + - + -

Electrical Gradient ↑
EQUILIBRIM
At this moment

Concentration
13 Gradient 7

- -
- + -
+ +
- - + +
+ - +
+
- +
- + + EQUILIBRIM
- + - +
+ +
- - -
- + -
+ +
- + - + -

Electrical Gradient

Concentration gradient = Electrical gradient


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In the beginning

Concentration
Gradient

- -
+

- + +
-
+
- +

Only “great” Concentration gradient

No Electrical gradient yet


With time

Concentration
Gradient

- -
+

- + +
-
+
- +

Electrical Gradient

Electrical gradient develops and gradually ↑

Concentration gradient ↓
Does this mean no movement
At the End
across the membrane???
Electrochemical Equilibrium

Concentration
Gradient

- -
+

- + +
-
+ +
-

Electrical Gradient

Concentration gradient Electrical gradient


Concentration gradient Electrical gradient

NO further NET
movement of ion

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0
Charges are unequally
separated across the membrane - +

- -
+ Equilibrium
- + + Potential
of
-
+ +
-

Membrane has potential (Vm)


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Vm … in the Body
❑ Electrical charges in the body are carried by ions

o Anions; large intracellular proteins (A-), Cl-

o Cations; Na+, K+

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Resting Membrane Potential (RMP)

❑When the cell is not sending electrical signals


(i.e., at rest)

❑All body cells have a resting membrane


potential

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Excitable Cells
❑ ONLY Excitable Cells are able to change RMP,
 (can be stimulated to create an electric current)

Nerve cells (neurons) Muscle cells 40


Membrane Potential, in the Body
❑ 2 factors:
Concentration (mmol/L)

1. Unequal distribution Ion Extracellular Intracellular


of ions (ECF) (ICF)
Na+ 150 15
K+ 5 150
A- 0 65

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Membrane Potential, in the Body
❑ 2 factors:
K+
Na+
Na+
2. Selective permeability of Na+
K+
plasma membrane K+
Na+
ECF
✓ At rest, K+ >>> Na+ K+
A- ICF
Na+
K+ K+

✓ Large intracellular proteins K+


Na+

K+ K+
(A-) don’t leave ICF
Na+ Na+

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ECF
K+
Na+
+ + + + + + + + + + +
Membrane

- - - - - - - - - - -
-
ICF
K+ A Na+

Inside of the plasma membrane is always


negative with respect to outside at rest
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0 mV
- 70 mV + 70 mV

Reference
electrode Voltmeter Recording
ECF electrode
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

---------------------------------------------------------------------------------------------
Clker

ICF

Neuronal cell

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0 mV
- 70 mV + 70 mV

Reference
electrode Voltmeter Recording
ECF electrode
---------------------------------------------------------------------------------------------

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Clker

ICF

Neuronal cell

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The sign always designates the polarity of the
excess charge on the inside of the membrane

Which is greater in magnitude,


???

+ 70 mV or - 70 mV membrane potential?

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RMP in various cell types
epithelial cells
-60 mV

-53 mV
-10 mV

-90 mV
fibroblast adipocytes

-70 mV
-20 to -30 mV -58 mV
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Role of Plasma Membrane

Maintaining
Selective passage
separation of ions

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1. Sodium–potassium pump (Na+/K+ ATPase)

ECF

Na+/K+
Pump

ICF

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2. Diffusion of Na+ & K+ through their ion channels
(Leak channels)

ECF
Na+ Leak Channel

K+ Leak Channel
ICF

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1. Sodium – Potassium Pump

Active transport mechanism (requires energy “ATP”)

❑ Pumps 3 Na+ out for every 2 K+ in


❑ Participates in 20% of the membrane potential

 Unequal transport

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2. Diffusion of Na+ & K+ through leak channels

Each ion diffuse according to its


electrochemical gradient

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0

- +
As only + charges
cross the membrane
then the Vm is the
- -
+

- + +
Equilibrium
-
+ + Potential of
-

Membrane has potential (Vm)


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The potential measured when

Concentration gradient = Electrical gradient for that ion

Eion

EK+ ENa+ ECa2+ ECl-

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Equilibrium Potential of K+ (EK ) +

K+

K+

ECF
K+ Leak channel

Concentration
gradient
K+
ICF K+ K+
A- K+
K+ K+ K+ K+
K+
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Equilibrium Potential of K+ (EK ) +

K+ K+
K+
K+
K+ K+
K+
K+ K+

Electrical
gradient
ECF
K+ Leak channel

Concentration
gradient
ICF
A-
-90 mV K+ K+
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Equilibrium Potential of Na+ (ENa ) +

Na+ Na+
Na+ Na+

Concentration
Na+
Na+

gradient
Na+ Na+
Na+
Cl-
ECF
Na+ Leak channel

ICF

Na+ Na+
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Equilibrium Potential of Na+ (ENa ) +

Na+ Na+
Na+ Na+

Concentration
Cl-

gradient
ECF

Na+ Leak channel

Electrical
gradient
ICF

Na+ Na+ Na+ Na+

+ 60 mV Na+
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Calculation of Ion Equilibrium Potential

RT [X]o
Eion = ln Nernst Equation
zF [X]i

• Eion. is the equilibrium potential (Nernst potential) for a given ion. Note that the unit of Veq. is the
Volt. However, the equilibrium potential is typically reported in millivolts (mV).
• R is the universal gas constant and is equal to 8.314 J.K−1.mol−1 (Joules per Kelvin per mole).
• T is the temperature in Kelvin (K = °C + 273.15).
• z is the valence of the ionic species. For example, z is +1 for Na+, +1 for K+, +2 for Ca2+, −1 for Cl−, etc.
Note that z is unitless.
• F is the Faraday's constant and is equal to 96,485 C.mol−1 (Coulombs per mole).
• [X]out is the concentration of the ionic species X in the extracellular fluid. Note that the concentration
unit must match that of [X]in.
• [X]in is the concentration of the ionic species X in the intracellular fluid. Note that the concentration
unit must match that of [X]out.
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Concentration
of the ion
“outside”

Concentration
of the ion
Charge of
“inside”
the ion

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Calculation of Ion Equilibrium Potential

In a neuronal cell (having only Na+):


Na+ ECF = 150 mmol/L
Na+ ICF = 15 mmol/L

61 150
Vm = x Log10 = 61 x Log10 (10)
+1 15
= 61 x 1

Vm = 61 mV = E Na +

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If there is ONE ion in the cell

Membrane Potential (Vm) = Nernst Potential (Eion)

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Resting Membrane Potential (RMP)

At rest, all cells have a negative internal charge and unequal


distribution of ions, resulting from:

Limited Na+ permeability High K+ permeability


through Na+ leak channels through K+ leak channels
(high outside) (high inside)

Na+/K+ pump
(3Na+ out vs. 2K+ in)
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If there are more than one type of channels
that are open at any given time

Goldman-Hodgkin-Katz (GHK) equation

p is the relative membrane permeability for the ion


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61 log10

Goldman-Hodgkin-Katz (GHK) equation

For a typical neuron at rest:

pK : pNa : pCl
1 : 0.05 : 0.45
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The END

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