Ionic Basis of Membrane Potential

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					          Ionic Basis of Membrane Potential




                               Dr Sergey Kasparov
                      School of Medical Sciences, Room E9

Teaching home page:
Teaching home page:
http://www.bristol.ac.uk/phys-pharm/personal/virallab/teaching/downloads.php
http://www.bristol.ac.uk/phys-pharm/personal/virallab/teaching/downloads.php
 1.Phospholipid bi-layer is the key component of all cellular
 membranes.




Water (aqueous) phase:
Water (aqueous) phase:                             Water (aqueous) phase:
                                                   Water (aqueous) phase:
charged, polar molecules and
charged, polar molecules and                       charged, polar molecules and
                                                   charged, polar molecules and
ions can dissolve and move.
ions can dissolve and move.                        ions can dissolve and move.
                                                   ions can dissolve and move.
                          Lipid (hydrophobic) phase:
                          Lipid (hydrophobic) phase:
                          charged, polar molecules
                          charged, polar molecules
                          cannot dissolve and move.
                          cannot dissolve and move.
2.Bioelectricity is generated by the ions moving across cellular
membranes.

     Concentration of selected solutes in intracellular fluid and
     Concentration of selected solutes in intracellular fluid and
                  extracellular fluid in millimols
                  extracellular fluid in millimols
mM 160
mM 160

   140
   140

   120
   120

   100
   100
                                                                          Inside the cell
                                                                          Inside the cell
    80
    80

    60
    60                                                                    In extracellular
                                                                          In extracellular
                                                                          fluid
                                                                          fluid
    40
    40

    20
    20

    0
    0
                                                          in o atte
                         g 22++




                                                            oa e
                                   a 22++
                 a ++
         K ++




                                                                  i ds
                                                                  Cl -




                                                                      e



                                                                  eiin
                                                           G ds
                                                  ga HC l -




                                                                   se
                                                                  ha




                                                                     n
                                                                    P
                Na

                        Mg
         K




                                  Ca




                                                                  os
                                                       c P 3 --




                                                                 TP
                                                                   C



                                                     A m sp h




                                                                   e
                N




                                                                 ci
                        M




                                                               AT
                                  C




                                                                  3




                                                               co
                                                      A o sp




                                                               ott
                                                               ac
                                                               O




                                                               A
                                                             lu c




                                                               o
                                                     ni CO




                                                              u



                                                            Pr
                                                            ho




                                                            Pr
                                                           Gl
                                                           H




                                                           n
                                                          Ph

                                                        mi
                                                     ni c
                                                  ga
                                               orr
                                            IIn o
                                              n
Remember these numbers (they may vary to some extent in different cells)



                           IN        OUT
             K+
              +           140           4
           Na+
             +             15          145

           Ca2+
             2+         0.001          1.8

            Cl--             4         115


                   CONCENTRATIONS ARE IN MILLIMOLS
                   CONCENTRATIONS ARE IN MILLIMOLS
If the membrane was freely permeable to these ions…




    their concentration would be identical on both sides.
3. Ions cannot pass through the membranes – they are too hyrdophylic for
3. Ions cannot pass through the membranes – they are too hyrdophylic for
that. Therefore they use channels – special proteins embedded into the
that. Therefore they use channels – special proteins embedded into the
plasma membrane.
plasma membrane.
       Forces which determine the direction of transport
                     across the membrane
                       Passive vs active transport
   Passive                               Active
   - along the concentration             – uses energy supplied by the
   gradient and using the energy of      cell to special proteins called
   this gradient                         PUMPS
                                         - against the concentration
                                         gradient




It is the pumps which are responsible for the generation of These guys are
                                                            These guys are
ionic gradients across the membranes of neurones             called pumps!
                                                             called pumps!
        Chemical vs Electrical Driving Force




Chemical driving force
                        Chemical vs Electrical Driving Force




                                                          _
                            +           +       +         _                        +           +
                    +
                                                +         _                    +
    +                                                     _    +
                                                +         _
                +               +
                                            +
                                                +         _                +           +
                                                                                                   +
+
                                                +         _+
                                                          _
                +                               +         _                +
                                +
                                                +         _                            +
                                            +   +         _                                        +
        +
                                                +         _        +
                                                          _
                                    +           +         _
            +                                   +         _            +                   +
                                                +         _
                                                +         _




                                        Electrical driving force
_
_                        +           +       +
_                    +
                                             +
_    +
_                                            +
_                +           +
                                         +
                                             +
_+                                           +
_
_                +                           +
_                            +
                                             +
_                                        +   +
_        +
                                             +
_
_                                +           +
_            +                               +
_                                            +
_                                            +
   Chemical and Electrical Driving Forces may combine to
         create the Electrochemical Driving Force

            +
         +_ _ +               +
                                  4mM
      +_      _
                  +       _+               Chemical driving force
  +_                              +
         +    +       +     _
+ _               +       +   +
         +                  _
   _ +       140 mM  +    +
+      +           _
    _         +      +        Electrical driving force
                 +
  + _  +  +
                 _
   + _ -70 mV _ + What will happen if the potential of this
         _ _         membrane decreases to -10 mV?
     +          +      Chemical driving force
         + +
             K+
              +




                                  Electrical driving force
  Conclusion: movement of charged particles
such as ions, across the membrane depends on
electro-chemical driving force (the sum of the
force generated by chemical gradient and the
      force generated by electric field).
Chemical driving force




Electrical driving force   _
                           _                                           +       +
                                                    +
                                +
                           _                                                   +
                           _                    +                          +
                                                                               +
                           _+
                                                +                              +
                           _
                                        +
                                                                               +
                                                                           +
                           _        +
                                                                               +
                           _                +
                                                                   +

                           _                +           Net flux               +
                           _                +
                                                                               +



                                                                       V
Chemical driving force




Electrical driving force   _
                           _                                           +       +
                           _                        +
                                                                               +
                                                                               +
                           _
                           _    +
                                                                               +
                           _
                           _+                   +                          +   +
                                                                               +
                           _
                           _                                                   +
                           _
                           _                                                   +
                           _
                           _            +
                                                +                              +
                                                                               +
                           _
                           _                                                   +
                           _                                               +
                                                                               +
                           _        +
                                                                               +
                                                                               +
                           _
                           _                +
                                                                   +           +
                           _                +           Net flux               +
                           _                                                   +
                           _                +
                                                                               +


                                                                       V
Chemical driving force




Electrical driving force   _
                           _                                           +       +
                           _    +
                                                    +
                                                                               +
                           _                                                   +
                           _
                           _+                   +                          +
                                                                               +
                           _                                                   +
                           _
                           _                    +                              +
                           _
                                        +
                                                                               +
                                                                           +
                           _        +
                                                                               +
                           _
                           _                +
                                                        Net flux   +           +
                           _                +                                  +
                           _                                                   +
                                            +
                                                                               +


                                                                       V
The Reversal Potential:
Potential of the membrane at which the
electrical driving force is exactly equal the
chemical driving force and therefore
THE NET FLUX of this particular ion is NIL.


       Reversal potential can be calculated using Nernst equation:




                      Eion = 61.5mV      Log (Cout /C   in)
                                 Z
 61.5 is a calculated constant derived from Universal gas constant, the
 temperature (37oC) and Faraday electrical constant
 Z – is a valence of an ion
                      Using this equation:

                ENa = 61.5/1 * log (145/15) ≈ 60.5 mV
                 Na




                EK = 61.5/1 * log (4/140)
                 K                              ≈ -95 mV


This means that in a hypothetical neurone sodium flux through the
open channels will tend to bring membrane potential toward +60.5
mV, while potassium flux will bring it toward -89 mV.


 But this could only happen if these ions were allowed to freely flow
 But this could only happen if these ions were allowed to freely flow
 through the membrane… and they are not!
 through the membrane… and they are not!
Because the membrane is essentially impermeable to ions, they have
to use ion channels to pass between intra- and extracellular space.




       A leak channel
       A leak channel                     A gated channel
                                          A gated channel
1. When neurone is at “rest” its membrane potential is negative, this is
called “resting membrane potential”.
2. At rest the main ion flux is K+, but also there are small Na+ and Cl--
                                 +

fluxes. Since the potential at “rest” does not change, it means that the
sum of these currents is zero.
3. Permeability of the membrane to an ion (NOT actually the membrane
but the channels passing that particular ion) may vary, because the
channels may open and close.

The equation which takes into account impacts of all these 3 ions and
predicts the resting membrane potential is called “Goldman-Hodgkin-
Katz” or “Goldman” or “Constant Field” equation.



     Vm = 61.5 mV x log ( P
                                   PK [Kout] +PNa[Naout] + PCl[Clin]
                                     K   [Kin] +PNa[Nain] + PCl[Clout   ]
                                                                          )