Computer model of hydrated phospholipid bilayer ION CHANNELS  &  
MEMBRANE POTENTIALS
Membrane Transport :   

How Things Get Across a Membrane

4 Ways:

1. by DISSOLVING in a membrane   fig
2. by membranes ENGULFING particles   fig
3. by CARRIER PROTEINS   fig
4. by CHANNEL PROTEINS via diffusion

 


       

 

 

 

 

 

 Skip this material move to Ion Channels

1. by DISSOLVING in a membrane
  
     hydrophobic solutes into a lipid bilayer
          
         Partition vs. Permeability Coefficients [ see fig ]

2. by membranes ENGULFING particles
        movement of large volumes of solute via membrane vesicles

  
     Bulk Transport
  
            Exocytosis [ 14.25 & 14.26 ]
  
                solute packaged membrane vesicles [endomembrane system] fuse
                    w plasma membrane releases bulk material to outside
  
            Endocytosis
  
                      uptake via invagination of exterior cell membrane packaging solutes
                    into interior membrane bound endocytotic vesicles
                    - phagocytosis - solid particle uptake by specialized cells… [ 14.27
 
                                       phagocytes [ macrophages & WBC 14.28 ]  = phagosomes (>250 nm)
  
                      - pinocytosis - liquid uptake into small vesicles (<150nm)
  
                      - receptor mediated endocytosis
  
                             LDL receptors (cholesterol) (14.29 & 14.18)

 

 

 

 

 

 

  

Membrane Transport : How Things Get Across a Membrane

3. by CARRIER PROTEINS [ 12.2
]
   
     protein receptors w specificity for a solute
   
     transport solute through a lipid bilayer
                [
bacteriorhodopsin - light mediated H+ transport 12.4

        CARRIER MEDIATED TRANSPORT
   
             Facilitated Diffusion   [ 12.6 ]
   
             Active Transport  (Na-Pumps & Proton Pumps)   [ 12.8 ]

4. by CHANNEL PROTEINS via diffusion [ 12.2 ]
   
     ions & small hydrophilics move thru a hydrophobic PORE
   
             Action Potentials  [ 12.30 ]    
                Synaptic Transmissions  [ 12.36 ]

 

 

 

 

 

 

 

 

 
Brief Review of Cell Membrane Transport

    Unit Membrane Hypothesis:
   
         "all membranes look alike in TEM"

    Current structural model - Fluid Mosaic model  [ fig 11.4 ]
   
          lipids     =  phospholipid bilayers   [ types of p-lipids fig 11.17 ]
            
proteins  =  [ fig 11.22 ]
                a)
Integral (intrinsic proteins)... denatured upon release
   
                b) Peripheral (extrinsic)... easily extractable

    Extra-cellular Matrix-
            glyco-proteins secreted by cell, i.e., "a cell wall"

 

 

 

 

 

 

 

Some Membrane Terminology…

    ION [ligand]…   atom or group of atoms carrying an electric charge;
            ions may exist in solid, liquid, or gaseous environments

            have flux rates proportional to lipid solubility (except water)

    CARRIER PROTEINS - intrinsic proteins
            transport solutes via small, conformational changes in protein shape - 
            move water soluble molecules

    TYPES or KINDS of SOLUTE TRANSPORT – [ 12.12 ]

   
         DIRECTIONAL
   
                 UNIPORT - one way
   
                 SYMPORT - two same way
   
                 ELECTROGENIC - one way, charged
   
                 ANTIPORT - two way, opposite directions
       
ELECTROCHEMICAL GRADIENT - driving force is established by
   
             a difference in (conc) or potential... on either side [ 12.7 ]

 

 

 

 

 

 

    PASSIVE Transport - solute movement w existing electrochemical gradient
        
               no energy is expended; movement toward equilibrium  [ 12.5 ]
   
         Diffusion - net random thermal motion of a solute [ hi --> lo ]
   
         Osmosis - net movement of water from [high] --> [low] [ 12.15 ]           
                       water movement...an anomaly; not lipid soluble, yet highly permeable

    ACTIVE Transport - solute movement against an existing electrochemical
                       gradient requires energy; movement away from equilibrium [
12.8 ]
     
     NaK-ATPase (Na Pump) - carrier actively Na out / K in [ 12.9 & 12.11 ]

    COUPLED Transport - transfer of one solute depends upon
   
             simultaneous transfer of 2nd solute [ 12.8 ]
   
     Na/Glucose cotransport [ 12.14  & 12.14 enhanced ]

    CARRIER MEDIATED Transport - Plants vs. Animals systems    [ 12.17 ]
   
     Animals - NaK-Atpase = Na gradient        Plants - H+ATPase = H+ gradient
              
         Na driven symport                               H+ driven symport
 
          H+ATPase (lysosomes)                          H+ATPase (vacuole) 

 

 

 

 

 

 

 

 

 

  Let's look at role channel proteins
  
  4. by CHANNEL PROTEINS via passive diffusion [ 12.2 ]
   
       ions & small hydrophilics can move thru a membrane hydrophilic PORE
        
ion channels are responsible for... Action Potentials           [ 12.30 ]   
 
                                                         ... Synaptic Transmissions  [ 12.36 ]

  ION CHANNELS and Transport
    
  an ion channel is a trans-membrane aqueous pore formed by a…

          CHANNEL PROTEIN - membrane transport proteins which 
                  forms a 
hydrophilic pore  allowing small molecules and ions
   
                   to move ions via passive uniport [in/out].       [ 12.2 & 11.25 ]
   
                                                 esp:     Na / K / Cl / Ca
  
   
        ROLE of Ion Channels
                  makes membranes
transiently permeable to charged ions 

   
                   opening of a channel allows rush (pulse) of electrical charge in/out

 

 

 

 

 

 

 

 

 

   PROPERTIES of Ion Channels    ("ionophores" = ion mover)

      SELECTIVE - permits only some ions to pass, and exclude others

   
  PORE SIZE - based upon distance between & distribution 
                      of polar charged aa's (glu, asp, his, lys, arg) on channel protein  [fig]
           
         often the sphere of hydration of the ions is shed to facilitate transport
   
         - positive channels:  allow - ions to flow  &  vice versa
              
Gramacidin model: cationic bacterial antibiotic ionophore [ Na+ ]
                              figure

      GATED - channels exist in OPEN/CLOSED conformation states   [ 12.22 ]
   
           VOLTAGE Gated  - open state controlled via cell potential 
   
           LIGAND Gated    - controlled by binding of solute    [ as acetylcholine ]
   
           STRESS ACTIVATED- as with a mechanical force  [ auditory hair cells ]

 

 

 

 

 

 

 

 

Observing Ion Channels in Action

  PATCH CLAMP  Recording...    Procedures  &  Equipment   &  [ 12.20 ]

        microelectrode  [μm meter glass tube]  contacts membrane surface
   
             vary concentrations of ions on either side or clamp voltage at set value
   
             records voltage changes across membrane
   
             current allows on/off as conformation of channel protein changes
                                    see fig 12.21

    Taste - an example of how ion channels work.   article  (Taste Fundamentals)
                   salty & sour taste are due to ion channels

    an Atomic Structural Model of a  K+ ion Channel

 

 

 

 

 

 

 

 


  MEMBRANE POTENTIAL...     [Cell's RESTING POTENTIAL]
       
- net distribution of ions across cell is often not equal
                i.e., a non-zero (neutral) distribution results in a
charge differential
   
     - leads to voltage differences [+/-] across membranes
   
     - the electric charge exhibited by most typical cells is [ - ] negative

  POTENTIAL - (in electrical terms) is amount of electrical charge 
                          at one point in an electric circuit compared to
                          some other point in the same circuit

            - measured inside vs. outside of cells - via microelectrode 
                   
SGA                              - 65 mVi
                    Frog muscle fibers         - 90 mVi
                    Nitella                          - 150 mVi
                    Valonia                          + 15 mVi

 

 

 

 

 

 

 

 

  

NERNST POTENTIAL     [equation - defines passive ion equilibrium]     (12.27)

                E (mv)  =  R T      ln [Co]    =   +/-  62 lg10  [Co]
   
                      zF          [Ci]                              [Ci]

   E(mv)  =  (1.98) (273 + 37)     (+/-1) (23,000)   [2.303]  =  0.062 lg10  [Co]
                                                                                                                      [Ci]

    Causes of Resting Potential - all which make inside of cell  ( - )     NernstEquation
   
         unequal distribution of the "sexy" ions (Na, K, Ca, Cl, H)
   
        active transport NaK-ATPase  =   3 Na(+)  out  &  2 K(+)  in
   
         differential permeability of Na (slower in)   &   K (faster out)
   
         lots of protein [anions -] inside cells
   
         diffusion of Cl- in faster than Na in                                     measured potential

 

 

 

 

 

 

 

 

 

  

ACTION POTENTIAL - a self-propagating change in the voltage 
        i.e., a
depolarization or reversal of resting potential charge across membranes

   
         name given to changes in electrical charges that occur during
   
         the stimulation of a nerve cell, usually visualized graphically
   
                 from an oscilloscope recording

    PROPERTIES of an AP
   
        requires a living cell, i.e., requires O2 for cell metabolism 
           eliminated by metabolic
poisons as cyanide

   
         measured using microelectrodes impaled into cells  [fig]
   
         has a threshold - amount of stimulus needed to "fire" an AP
   
          an "all-or-none-phenomena"
   
          rapid – has a time course = 2 to 3 msec

 

 

 

 

 

 

 

 

  

  EVENTS DURING an AP                                   visualization of AP                  
   
         depolarization - goes from negative to positive
   
                 voltage gated Na channel opens - Na floods in    [ 12.31  &  12.32 ]
                    potential goes from  -70mV  to  +35mV    (interior goes transiently + )

            repolarization - Na channels close & 
   
                 voltage gated K channels open - K floods out     [ ion channel changes ]   

            refractory period - time before another AP can 'fire'     [ summary figure ]

  CONDUCTION of an AP along an axon [ 12.33 ]
   
         local spreading of electric charge = change in Na channels
   
                 of adjacent membrane regions
   
         autocatalytic - "domino effect"  [ 12.33b ]

 

 

 

 

 

 

 

 

 

 

  
 
Post Synaptic Potential
   
     Synapse - functional connection between neurons [ 12.34 ]
   
          Synaptic cleft - space between neurons across
   
          Synaptic knob - site of synaptic vesicles that hold neurotransmitter (acetylcholine)

  Events
   
     pre-synaptic side
              AP reaches synaptic knob
   
             opens voltage gated  Ca+2  channel  (Ca floods in)   [ 12.35 ]
   
             synaptic vesicles fuse w presynaptic membrane
   
             release neurotransmitter into cleft
        post-synaptic side
- neurotransmitter binds to receptor  [ 12.36 ]
   
             postSM receptors are ligand gated ion channels
   
             ion channels open - change potential charge of
   
             post-synaptic membrane fires a new AP
   
     removal of stimulus = enzyme   (esterase)   destroys transmitter

 

 

 

 

 

 

 

 

  
  Synaptic Events & Neurotransmitters 
      
Excitatory neurons  -->  open Na/Ca channels PostSM -->  +  --> AP
        
      neurotransmitters include acetylcholine & glutamate...  
                                   
Chinese Restaurant Syndrome                 

                                                                                
      
Inhibitory neurons --> open Cl channels --> - --> no AP
   
             neurotransmitters are GABA and glycine       fig 12.37

Integration of stimuli....        fig 12.38

Effects of Drugs - 1) barbituates & tranquilizers (valium)
   
                                       bind to GABA-gated Cl channels  thus are inhibitory
   
         2) antidepressants (prozac) - blocks reuptake of serotonin (neurotransmitter)
   
          3) psycho active drugs (LSD/mescaline) -
   
                                bind to serotonin-dopamine brain cell receptors

 

 

 

 

 

 

 

 

  Neurotransmitters    (tbl 12.3 p 402) 
        neuro-muscular junction - acetylcholine (contractions)
        biogenic amines
(CNS) -  epinephrine & norepinepherine - increase heart rate
 
       
serotonin  &  dopamine - affect mood, attention & learning
        amino acids
- ASP & GLU - excitatory (CNS);    GLY & GABA - inhibitory

        pe
ptides - (small proteins) -  endorphins - decrease perception of pain 
                          substance P - excitatory transmitter - signaling pain 
   
Stimulants - chemicals that increase activity of CNS
   
     cocaine - prevents re-uptake of dopamine by synaptic vesicles pre-SM
   
     caffeine - can increases post-synaptic threshold (Cl in...  more - ...greater threshold )
                        also stimulates HR & breathing rate        (caffeine food contents)
   
     barbiturates & valium – intensifies GABA (inhibitory) effects
   
     Poisons like strychnine - prevent loss of transmitter  ---> muscle tetanus
 
Neuro-diseases & Transmitters 
   
      Parkinson's is due to a lack of dopamine
        schizophrenia is due to too much
dopamine

        depression is due to a reduced
epinephrine-norepinephrine

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