Cogs 107B  SYSTEMS  NEUROSCIENCE

 

TA: Flavia Filimon,  

e-mail address: ffilimon@cogsci(.ucsd.edu)

 

 

Note: handouts for week 1 are mostly based on Kandel, Schwartz and Jessell’s

            Principles of Neural Science, 2000 and Squire et al. 2003

 

 

Today:

1)      Ion Channels

2)      Resting Membrane Potential

3)      Action Potential

4)      Neurons and electrical equivalent circuits

5)      NMDA channels

 

 

1)     Ion Channels

 

-         ion channels are proteins that span the cell membrane

-         are important for signaling/ rapid information processing in the nervous system.

-         Properties of ion channels:       * conduct ions

    * recognize and select specific ions

    * open and close in response to specific electrical, chemical or mechanical signals

    

-         2 types of ion channels:

1)      resting

2)      gated

-         types of gated channels: 

1)      voltage-gated channels (changes in membrane potential).

2)      ligand-gated channels (neurotransmitter/ chemical binds to receptor)

3)      mechanically-gated channels (respond to pressure or stretch of membrane)

-         Resting channels are normally open during the resting state of the membrane, and are not influenced significantly by extrinsic factors , eg potential across membrane. They are important in maintaining the resting membrane potential

-         Gated channels are closed when the membrane is at rest.

-         Ion channels have at least 3 functional states:

·        closed and activatable

·        open (active)

·        closed and nonactivatable (refractory/ inactivated) – e.g. voltage-gated Na+ channels

-         Closing and opening of channels involves conformational changes, eg in one region, as a general structural change of the channel, or via a blocking particle (plug)

-         The transition of a channel between different (open or closed) states is called gating

-         The flux of ions through the ion channel is passive

-         The direction and eventual equilibrium of ion flux are determined by electrostatic  and diffusional driving forces across the membrane

à the electrical potential across the membrane

à the concentration gradient of the ions across the membrane

  

-         Ion channel selectivity: ions are surrounded by waters of hydration, i.e. clouds of water molecules. Ions with a smaller diameter (e.g. Na+ ) attract more water molecules, due to a more intense (more concentrated) local field strength. Ions with a larger diameter (e.g. K+) attract fewer ions due to a less localized charge and have a smaller effective diameter.  Ion channel selectivity is partly based on size and on binding at specific polar sites inside the channel.

 

 

2)     Resting Potential

 

-         results from separation of charges across membrane, which is due to:

§         1) a semi-permeable membrane (more resting K+ channels)

§         2) the Na+K+ pump

-         at rest: nerve cell has an excess of positive charge on the outside of the membrane, and an excess of negative charge on the inside

-         the usual range of the resting potential in neurons: -60 mV to -75 mV

-         Na+, Cl- , CA2+   à more concentrated outside the cell

-         K+, A-                   à more concentrated inside the cell

-         The resting membrane potential is determined by resting ion channels

-         All electrical signaling involves brief changes from the resting membrane potential due to alterations in the flow of electrical current across the cell membrane, which are caused by opening and closing of ion channels.

 

-         the initial concentration gradients are set up and maintained by the Na+ - K+ pump, which obtains energy through ATP hydrolysis. The sodium-potassium pump moves Na+ and K+ against their concentration gradients – it drives:

3 Na+ ions out and takes 2 K+ ions in.

 

-          Potassium:     Because K+ ions are more concentrated inside the cell, and because there are more resting K+ channels than resting Na+ channels, K+ will tend to diffuse from inside to outside the cell, down its concentration gradient. (!The resting membrane is more permeable – has more channels - to K+ ions).

-         At a certain point, the electrical force driving K+ into the cell exactly balances the chemical force driving K+ ions out of the cell.

-         This is called the potassium equilibrium potential, Ek, also known as the Nernst potential for K+

-         à Nernst Potential: the membrane potential at which there is no net flux of the particular ion species across the cell membrane

 

Species of Ion                         Equilibrium potential (mV) in squid giant axon/ mammalian neurons

     

                  K+                                                        -75 / -102

                  Na+                                                      +55 / +56

Cl-                                                       -60 / - 76          (these all depend on species of neuron, animal, etc.)

 

! Nernst potential = equilibrium potential = reversal potential (if the channel conducts just one type of ion) !

 

Q: what happens to potassium if the membrane potential is clamped to -120mV? What about -40 mV?

 

-         Sodium:    2 forces drive Na+ into the cell:

- concentration gradient (higher Na+ concentration outside than inside cell)

- the negative electrical potential difference across the membrane (outside of the cell is more positive than inside)

       à Na+ and K+ fluxes set the value of the resting potential – yet the membrane potential is not equal to either Ek or ENa; it lies between the two.

 

3)       Action Potential

 

-         when the membrane is depolarized past threshold (-45 to -55 mV):

-         rising phase of the action potential: voltage-gated Na+ channels open rapidly àthe net influx of positive charge causes further depolarization, causing more voltage-gated Na+ channels to open, etc. (= inward Na+ current - fast)

-         At the peak of the action potential, Vm approaches ENa (+55mV)

-         K+ efflux from resting channels continues throughout the depolarization

-         Falling phase: Na+ channels gradually close by the process of inactivation

-         Voltage-gated K+ channels open and cause and increase in K+ efflux (= outward K+ current - slow) à repolarization to resting potential

-         The continued open state of the voltage-gated K+ channels leads to the refractory period (absolute and relative) (afterhyperpolarization).

 

Q: what is the usefulness of refractory states? à prevent reverberation of action potentials between soma and dendrites

 

4)     Neurons as electrical equivalent circuits

 

-         conductors/ resistors: ion channels (and membrane)

-         batteries: concentration gradients of relevant ions

-         capacitors: membrane (stores charge)

-         V = IR    ( I= V/R   <-> I = Vg)

-         Bigger axon  à more capacitance (greater surface which can store charge)

           à less longitudinal resistance  (cf. a pipe)

           à less membrane resistance (more ion channels)

-         know circuit model of the dendrite! Might need to know how to draw or label one.

-         Know graphs of voltage & current flow across resistors, capacitors, series circuit vs. parallel circuit.

 

 

5)       NMDA channels

 

-         requires both ligand-binding (glutamate – to AMPA and NMDA receptors) and voltage-gating (depolarization removes Mg++ plug)

-         need to know how to test and induce LTP (long-term potentiation)

-         1) small pulse in presynaptic axons (which synapse onto target cell) – look at the size of the post-synaptic potential

-         2) apply tetanus to axons synapsing onto target cell

-         3) apply the initial test pulse to axons – postsynaptic response should be enhanced = LTP

 

Note: the same neurotransmitter might bind to different receptors. E.g. glutamate binds to both AMPA and NMDA channels.