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CHAPTERS 6 & 7

    Membrane Potential and Action Potential

•   Membrane Potential,
•   Distribution of ions in body fluids,
•   Contribution of various ions to membrane potential,
•   Nernst Equation
•   Resting Membrane Potential
•   Action Potential
Membrane Potential
Membrane Potential : The difference in ionic distribution between
inside and outside of cells which results in electrical potential
difference across the cell membrane.

                  Units of this potential are volts (millivoltes)

          o
      _
              +




      Voltmeter




                          _
                  +
                                          CELL
Charged Substances in Body Fluids
Many molecules in our body fluids have electrical charges due to the presence
of negative groups (e.g. phosphate, RCOO-) or positive groups such as RNH3+.
Also most mineral elements such as sodium, potassium, chloride, and calcium
(Na+, Cl-, K+, Ca++) present in our body fluids as ions.


      Positive Charges                             Negative Charges

                                                          _
           Na+                                       Cl

                                                                  -
           K+                                        HCO3

           Ca++                                               -
                                                     PO42 & Organic anions
           Mg++
                                                     Proteins
           RNH3+
Distribution of Main Charged

                                                  Substances in Body Fluids

              _                                                                     _        _
      Cl                                      _                                                     _
                                                                                _ FIXED
                                                                _
                                         Cl                Cl                       _
                               Na+                                                                              K+            K+
          _                                                                                                 _        _
     Cl                          Cl
                                         _
                                                           Na+              +       K+       K+                           _
                                                                          K                             _ FIXED
                           _
                  Cl                                                                                        _
Na+                                               Na+                     _         _
          Na      +
                                                                                         _K+
                                                   Na+                   _ FIXED
                                                                             _
                                                       _
                                                                     _                   _        _                      K+
     Na+                        Na+               Cl            Cl                                      _
                                                                          K+            _ FIXED
                                                                                            _               _        _        K+
                                                                                                                          _
                                                                                                        _ FIXED
                       _             _
  +               Cl            Cl
Na                                                Na+                                          K+           _
                                                                                +                                             K+
                                                                                K


                  ECF                                                                          CELL
Properties of Charged Chemicals
Distribution of various charges outside and inside the cell play a significant role
in cell function. Excitable cells such as muscle and nerve use this phenomenon to
generate and propagate electrical signals.
                                                      Electrical
      Like charges repel each other.          +       Force
                                                                      +
 This creates force at opposite direction
 of each charge.                              _       Electrical
                                                                      _
                                                      Force



     Opposite charges attract each other.              Electrical
                                                                        _
    The force of attraction between these      +       Force
    charges has the potential of creating
    force and hence performing work. This is
    called electrical potential.
Distribution of Charges
The membrane potential is due to small excess of negative ions inside
of the cell and small excess of positive ions outside of the cell.

The negative charges are attracted to the positive charges and they form
a thin layer of negative inside and positive outside of the cell.

The rest of intracellular and
extracellular fluid remain neutral.
Electrical Current
  The movement of electric charges is called current. The electric force between
  charges makes the charges flow producing current.

      Current depends on:

              1- Potential difference = E (voltage)

              2- The medium in which the charges move = R (resistance)
        The relationship is given by Ohm’s law:


                                 E
                             I =
                                 R

- Movement of ions through channels is referred to current (I).
- The Voltage (E) is the membrane potential.
- The cell membrane shows the highest resistance (R ) to ionic movements.
Membrane Potential
The difference in ionic distribution between inside and outside of the cell
results in a negatively charged intracellular compartment compared to the
positive extracelluar environment.

Membrane potential is produced by:

          1- The action of Na/K pump at the cell membrane.

          2- Proteins, ATP and other organic molecules in the
             cell are negatively charged (anions), and can not cross
             the cell membrane therefore this makes inside of the
             cell negative.

          3- Ion Channels which cause leakage of ions across the
             cell membrane.
1- The action of Na/K pump at the cell membrane is
   essential for the production of membrane potential.


Na/K pump is electrogenic; this
transporter causes a difference in ionic
distribution between inside and outside
                                             2
of the cell.
                                                         2
An important function of Na/K pump
is
to control the volume of the cells; this
transporter pumps 3 ions out and 2                       3
ions into the cell. By doing this it keeps   3
a balance in concentration of particles
between inside and outside of the cell
hence keeping cell volume controlled.
2- Organic anions are trapped inside the cell due to their large
size and negative charge:

Cell membrane phospholipid
bilayer does not allow these
molecules to pass through therefore
preventing these molecules from
exiting out of the cell.




                                                      High resistance

                       _     _
                                 _
                     _ FIXED
                         _
3- Ion Channels in The Cell Membrane
Permeability of the phospholipid bilayer to charged ions is very low (zero).
But special proteins in cell membrane can allow small ions to pass across it.
This is due to the presence of specific ion channels (integral proteins)
in the cell membrane.




  Properties of ion channels:
     - Selective (size, charge)
     - Gated / non-gated
Membrane Potential Can be Measured
The potential difference across the cell membrane can be
measured using microelectrodes and a sensitive voltmeter.


                                                        In some cells the membrane
                                                        potential can change.
Contribution of Various Ions to Membrane Potential
The unequal distribution of ions across the plasma membrane results in the
membrane potential. Each ion has a different contribution to the creation of this
membrane potential.
The degree of contribution of each ion to membrane potential depends on:

    1) Concentration difference of the ion

    2) Membrane permeability of the ion.
Membrane Potential
                    Non-gated K+
                    Channel
Sodium potassium                    K+
leak channels

                                   K+
                   Gated K+                      2 K+
                   Channel          _    _
                                             _
                                   _ FIXED
                                       _            ATP
      Na+          Na+

                                                        3 Na+
  Gated Na+
  Channel
Nernst Equation

                                                                     _
- In the body at 37 oC the electrical difference that balance the concentration difference of a
univalent ions such as Na+ can be determined by Nernst Equation:



                                                    C1
                       EMF (mV) = + 61 log
                                                    C2


EMF = Electromotive force between side 1 and 2 of a membrane,
C1 = concentration on side 1
C2 = concentration on side 2.
Nernst Equation:
                                                C1
                       EMF (mV) = + 61 log
                                                C2




                                          +                   _

                                                         140 mM K+


                                                         14 mM K+

This means that 61 mV negative charges inside of the cell is required to keep the
above concentration difference of K+ between inside and outside of the cell. Assuming
that the cell membrane is highly permeable to K+.
Resting Membrane potential
- In excitable cells the potential difference between inside and outside of the cell
during rest is called “resting membrane potential” (r.m.p.)


 Excitable cells:
           - Nerve cells
           - Muscle cells
           - Some endocrine cells
           - Some immune cells
           - Some reproductive cells

Change in r.m.p occurs in these excitable cells to perform a function.
Usually
this change indicate a signal. For example nerve cells produce signals and
propagate them by undergoing changes in their r.m.p.
Resting Membrane potential (Nerve Cell)
- During rest in nerve cell negativity of inside of the cell is maintained at (-60 to -90 mV).
- This results from the difference between concentrations of Na+ and K+ inside and outside
 of the cells which produces a potential difference across the membrane.




   Na+ 145 mM        12 mM

     K+ 5 mM         150 mM                   _      _
                                                         _
                                           _ FIXED
                                               _




                                                             Membrane potential = -75 mV
Magnitude of resting membrane
                potential in Nerve cells
- The magnitude of r.m.p. for large nerve cells is -90 mV negative inside.

 The factors that determine this potential are:

         1- Na/K pump

         2- Leakage of Na and K through the nerve cell membrane:

                  a- Contribution of the K diffusion

                  b- Contribution of Na diffusion



In large nerve cells the potential caused only by K+ and Na+ diffusion
is approximately -86 mV. The other -4 mV potential is due to the action of
Na/K pump.
Diffusion through Na+ and K+ channels contribute to about - 86 mV.
     Na/K pump contributes about -4 mV.

                                                        Na142            K4
                                     C1
           EMF (mV) = + 61 log                          Na14             K140
                                     C2




Because there are 75 to 100 times more K leak channels than Na leak channels
therefore the sum of potential is -86 mV. The rest ( -4 mV) is contribution by Na/K pump.
Action Potential
Action potential is referred to the change in membrane potential in
excitable cells. The change in the membrane potential is due to
movement of ions in and out of the cell.




               Na+ 142 mM                   K+ 4 mM

               14 mM        _       _       140 mM
                                        _
                          _ FIXED
                              _

                       Nerve cell
                                                     Membrane potential = -90 mV
  Axon of
A nerve cell
Ionic Movements During Action
          potential

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  • 1. CHAPTERS 6 & 7 Membrane Potential and Action Potential • Membrane Potential, • Distribution of ions in body fluids, • Contribution of various ions to membrane potential, • Nernst Equation • Resting Membrane Potential • Action Potential
  • 2. Membrane Potential Membrane Potential : The difference in ionic distribution between inside and outside of cells which results in electrical potential difference across the cell membrane. Units of this potential are volts (millivoltes) o _ + Voltmeter _ + CELL
  • 3. Charged Substances in Body Fluids Many molecules in our body fluids have electrical charges due to the presence of negative groups (e.g. phosphate, RCOO-) or positive groups such as RNH3+. Also most mineral elements such as sodium, potassium, chloride, and calcium (Na+, Cl-, K+, Ca++) present in our body fluids as ions. Positive Charges Negative Charges _ Na+ Cl - K+ HCO3 Ca++ - PO42 & Organic anions Mg++ Proteins RNH3+
  • 4. Distribution of Main Charged Substances in Body Fluids _ _ _ Cl _ _ _ FIXED _ Cl Cl _ Na+ K+ K+ _ _ _ Cl Cl _ Na+ + K+ K+ _ K _ FIXED _ Cl _ Na+ Na+ _ _ Na + _K+ Na+ _ FIXED _ _ _ _ _ K+ Na+ Na+ Cl Cl _ K+ _ FIXED _ _ _ K+ _ _ FIXED _ _ + Cl Cl Na Na+ K+ _ + K+ K ECF CELL
  • 5. Properties of Charged Chemicals Distribution of various charges outside and inside the cell play a significant role in cell function. Excitable cells such as muscle and nerve use this phenomenon to generate and propagate electrical signals. Electrical Like charges repel each other. + Force + This creates force at opposite direction of each charge. _ Electrical _ Force Opposite charges attract each other. Electrical _ The force of attraction between these + Force charges has the potential of creating force and hence performing work. This is called electrical potential.
  • 6. Distribution of Charges The membrane potential is due to small excess of negative ions inside of the cell and small excess of positive ions outside of the cell. The negative charges are attracted to the positive charges and they form a thin layer of negative inside and positive outside of the cell. The rest of intracellular and extracellular fluid remain neutral.
  • 7. Electrical Current The movement of electric charges is called current. The electric force between charges makes the charges flow producing current. Current depends on: 1- Potential difference = E (voltage) 2- The medium in which the charges move = R (resistance) The relationship is given by Ohm’s law: E I = R - Movement of ions through channels is referred to current (I). - The Voltage (E) is the membrane potential. - The cell membrane shows the highest resistance (R ) to ionic movements.
  • 8. Membrane Potential The difference in ionic distribution between inside and outside of the cell results in a negatively charged intracellular compartment compared to the positive extracelluar environment. Membrane potential is produced by: 1- The action of Na/K pump at the cell membrane. 2- Proteins, ATP and other organic molecules in the cell are negatively charged (anions), and can not cross the cell membrane therefore this makes inside of the cell negative. 3- Ion Channels which cause leakage of ions across the cell membrane.
  • 9. 1- The action of Na/K pump at the cell membrane is essential for the production of membrane potential. Na/K pump is electrogenic; this transporter causes a difference in ionic distribution between inside and outside 2 of the cell. 2 An important function of Na/K pump is to control the volume of the cells; this transporter pumps 3 ions out and 2 3 ions into the cell. By doing this it keeps 3 a balance in concentration of particles between inside and outside of the cell hence keeping cell volume controlled.
  • 10. 2- Organic anions are trapped inside the cell due to their large size and negative charge: Cell membrane phospholipid bilayer does not allow these molecules to pass through therefore preventing these molecules from exiting out of the cell. High resistance _ _ _ _ FIXED _
  • 11. 3- Ion Channels in The Cell Membrane Permeability of the phospholipid bilayer to charged ions is very low (zero). But special proteins in cell membrane can allow small ions to pass across it. This is due to the presence of specific ion channels (integral proteins) in the cell membrane. Properties of ion channels: - Selective (size, charge) - Gated / non-gated
  • 12. Membrane Potential Can be Measured The potential difference across the cell membrane can be measured using microelectrodes and a sensitive voltmeter. In some cells the membrane potential can change.
  • 13. Contribution of Various Ions to Membrane Potential The unequal distribution of ions across the plasma membrane results in the membrane potential. Each ion has a different contribution to the creation of this membrane potential. The degree of contribution of each ion to membrane potential depends on: 1) Concentration difference of the ion 2) Membrane permeability of the ion.
  • 14. Membrane Potential Non-gated K+ Channel Sodium potassium K+ leak channels K+ Gated K+ 2 K+ Channel _ _ _ _ FIXED _ ATP Na+ Na+ 3 Na+ Gated Na+ Channel
  • 15. Nernst Equation _ - In the body at 37 oC the electrical difference that balance the concentration difference of a univalent ions such as Na+ can be determined by Nernst Equation: C1 EMF (mV) = + 61 log C2 EMF = Electromotive force between side 1 and 2 of a membrane, C1 = concentration on side 1 C2 = concentration on side 2.
  • 16. Nernst Equation: C1 EMF (mV) = + 61 log C2 + _ 140 mM K+ 14 mM K+ This means that 61 mV negative charges inside of the cell is required to keep the above concentration difference of K+ between inside and outside of the cell. Assuming that the cell membrane is highly permeable to K+.
  • 17. Resting Membrane potential - In excitable cells the potential difference between inside and outside of the cell during rest is called “resting membrane potential” (r.m.p.) Excitable cells: - Nerve cells - Muscle cells - Some endocrine cells - Some immune cells - Some reproductive cells Change in r.m.p occurs in these excitable cells to perform a function. Usually this change indicate a signal. For example nerve cells produce signals and propagate them by undergoing changes in their r.m.p.
  • 18. Resting Membrane potential (Nerve Cell) - During rest in nerve cell negativity of inside of the cell is maintained at (-60 to -90 mV). - This results from the difference between concentrations of Na+ and K+ inside and outside of the cells which produces a potential difference across the membrane. Na+ 145 mM 12 mM K+ 5 mM 150 mM _ _ _ _ FIXED _ Membrane potential = -75 mV
  • 19. Magnitude of resting membrane potential in Nerve cells - The magnitude of r.m.p. for large nerve cells is -90 mV negative inside. The factors that determine this potential are: 1- Na/K pump 2- Leakage of Na and K through the nerve cell membrane: a- Contribution of the K diffusion b- Contribution of Na diffusion In large nerve cells the potential caused only by K+ and Na+ diffusion is approximately -86 mV. The other -4 mV potential is due to the action of Na/K pump.
  • 20. Diffusion through Na+ and K+ channels contribute to about - 86 mV. Na/K pump contributes about -4 mV. Na142 K4 C1 EMF (mV) = + 61 log Na14 K140 C2 Because there are 75 to 100 times more K leak channels than Na leak channels therefore the sum of potential is -86 mV. The rest ( -4 mV) is contribution by Na/K pump.
  • 21. Action Potential Action potential is referred to the change in membrane potential in excitable cells. The change in the membrane potential is due to movement of ions in and out of the cell. Na+ 142 mM K+ 4 mM 14 mM _ _ 140 mM _ _ FIXED _ Nerve cell Membrane potential = -90 mV Axon of A nerve cell
  • 22. Ionic Movements During Action potential