C2006/F2402 -- 2006 --Outline of Lecture #17 –
Electrical Communication #1
(c) Stuart Firestein,
Columbia University, New York, NY.
Last update 03/30/2005 05:07 PM .
Notes by Chris Kelly
1. Neurons: structure
- The brain –– why is it so special?
- We connect it with our idea of “self” and believe
personality resides there.
- Tremendous diversity of cell types and structures.
- Retains plasticity (an ability to modify itself)
- As the brain undergoes experiences and
environmental conditions, it changes itself to adapt.
- Despite this, the brain is the most developed
of organs, meaning that its cells are among the most differentiated.
Remember that neurons do not divide –– they are permanently in G0
- The main function: information transfer and
- The basic circuit: the body encounters a stimulus,
peripheral nerves produce an afferent (incoming) signal that comes into
the brain (or spinal cord) for processing. The result is an efferent
(outgoing) signal, carried through nerves, to some target, resulting in
a behavioral response.
- You step on a thumbtack, a pain signal goes to
the spinal cord, contacts a motorneuron, signal goes out to the leg
muscle, leg retracts.
- Two major divisions: central nervous system
(CNS) and peripheral nervous system (PNS).
- CNS: brain and spinal cord.
- PNS: everything else (motor neurons, sensory
- There are a few exceptions: the retina, for
example, is in the back of the eye but is considered part of the
- The functional unit is a neuron.
- There are 1011 neurons in the adult
- Neurons were not always recognized as distinct
cells: until Ramon y Cajal proved otherwise, people believed there was
one big interconnected “nerve net.”
- Neurons can be extremely large (up to 40 meters
long in a whale) or extremely small.
- There are two main consequences of Ramon y Cajal’s
discovery that nerves are distinct units:
- 1) The law of dynamic polarization:
information only moves in one direction down a neuron (most of the
- 2) Specific connectivity: the specificity of
the connections in the nervous system is critical. Think of the
wires behind your stereo.
- Glial cells are support cells in the brain.
- Glial cells are not involved in signaling; rather,
they provide structure, dole out trophic factors, regulate metabolism,
contribute to immune response, construct the blood-brain barrier, etc.
- FYI: There are several kinds of glial cells:
astrocytes, Schwann cells, oligodendrocytes are a few.
- There are 1012 glia in the brain –– a
full order of magnitude more than neurons.
- Major parts of the neuron, common to nearly all
- Soma / cell body: site of protein
synthesis, metabolism, etc.
- Dendrites (Gr: tree): protoplasmic
extensions continuous with the cytosol. These branch and divide, thereby
sending projections all over a tissue, and thin as they extend.
- Axon: A long cable that extends from the
soma but is functionally distinct from it. If you look at the plasma
membrane of an axon, you see that it contains lipids different from
those in the soma’s membrane. The axon may branch out, but it remains
isodiametric in all of its projections. If a neuron is particularly
large, as in the whale, it is because its axon is long.
- Synaptic terminal: sometimes referred to as
the “bouton.” It is the end of the axon that contacts a dendrite,
- We can now revisit the dynamic polarization
principal of Cajal.
- Information enters the dendrites, travels through
the tree to the soma, then (if it meets the threshold) enters the axon,
and travels its length until the synaptic terminal, which then passes
the signal to the next cell.
II – Membrane Potential
- We keep referring to a “signal” –– what is it?
- A signal is encoded as changes in membrane
- Membrane potentials
- Refers to voltage created when the cell separates
charges on opposite sides of the membrane. It puts work into separating
opposite charges, thereby creating potential energy as voltage.
- Voltage always refers to two points: i.e. here
with respect to there. “There” is usually ground; in physiology, ground
is the outside of the cell. So, voltage refers to the inside of the cell
with respect to the (neutral) outside.
- If the cell’s potential is –50 mV, then the
cell is negative with respect to the surround interstitium.
- How can you measure potential?
- Use an electrode.
- An electrode is an extremely thin glass
capillary with an open tip that is about one micron in diameter. You
fill the electrode with a conducting salt solution and insert a wire
connected to a voltmeter. You then poke the electrode through the
cell membrane and measure the intracellular potential against that
- This method reveals that neurons usually
have negative resting membrane potentials, between –50 and –90
mV. This potential is often referred to as Vm.
- What constitutes and creates this resting membrane
- In electronics, potentials and current come the
position and movement of electrons. In cells, we are not concerned with
electrons, but with ions.
- Common ions involved in establishing Vm:
- Sodium (Na+)
- Potassium (K+)
- Calcium (Ca++)
- Chloride (Cl-)
- How does the potential arise?
- The cell maintains an asymmetric distribution of
ions across the membrane and makes the membrane selectively permeable.
Both of these merit further discussion.
- Asymmetric distribution:
- Plasma membrane is lipids, so charged
particles cannot pass through unless it’s through a pump (like the
Na/K ATPase) or channel.
- A typical distribution is:
- Other ions involved
- Inside: negatively-charged proteins,
- Outside: chloride, calcium
- Just having this distribution is not enough,
however: we still haven’t created any potential. Potential only arises
when SOME of the ions can get through the membrane. This is achieved
through having selectively permeable channels in the
- Let’s say we poked some holes in the membrane
that only permeated potassium … NOT sodium.
- The first response will be for potassium
to flow down its concentration gradient, out of the cell.
- This outward flow leaves behind unpaired
anions within the cell, though. Eventually, the negative charge
inside the cell will become so great that the diffusive force on
the potassium ions, directed outward, will be outweighed by the
electrical force on the potassium ions, directed inward to the
negatively charged cytosol. An equilibrium condition is then
created where the number of ions leaving the cell equals the
number of ions entering the cell.
- We can then say that potassium has reached
an equilibrium condition, which has an associated electronic
potential, measured as EK= -75 mV.
- We can make a similar calculation for
sodium, if we make the cell selectively permeable to sodium
ONLY: ENa= +50 mV.
- Think about where the diffusive
force will drive sodium, and where the electrical force will
drive it. Refer to the concentrations above.
- Both of these values can be obtained with
the Nernst equation. See your textbook if you are interested in
- If we measure the resting membrane potential of a
neuron, we see it is around –50 mV. This is between the equilibrium
potentials for potassium and sodium, but closer to that of potassium.
So, we see that the cell is mostly permeable to potassium, but also
slightly permeable to sodium.
- What would the RMP (resting membrane
potential) be if the situation were reversed, if the cell were more
permeable to sodium than to potassium?
- The RMP of a cell, then, is found by individually
weighting the equilbrium potentials of the various ions involved, based
on the membrane’s permeability to each one. Then you just add. This is
quantified by the GHK (constant field) equation; see book for details if
- So far, we have referred to selective permeability
without discussing how it arises. The cell creates it with ion channels.
- Ion channels are sophisticated transmembrane
proteins that form a selective aqueous pore in the membrane. The
channels have some important properties:
- 1) They are highly selective.
- Channels become selective by varying their
shape/size and flanking certain regions of the pore with
positive or negative charges. The degree of selectivity can
vary: some only let cations through; others only let potassium
through. See book for details.
- 2) They have a specific degree of conductance.
- Some are fairly big and allow lots of ions
through; others are smaller.
- 3) They are gated.
- In order to control the membrane
potential, the neuron must be able to control the open/closed
status of its various channels. For now, we will only consider
voltage-gated channels (i.e. channels that only open when faced
with a certain voltage range); in synaptic signaling, we will
see the importance of ligand-gated channels.
- How do you detect these ion
channels? They are too small to be seen. Instead, scientists use a method
known as patch clamping.
- One applies a glass
electrode, as described above, to the membrane of a cell. Applying a
little bit of suction causes a piece of the membrane to become attached
to the electrode; one can then pull off the electrode and take the
membrane section with it. Because the seal between the electrode and the
membrane piece is very tight, one can then treat the inside of the
electrode and the bath in which you place it as different sides of the
- Once you have isolated one
or two channels in your membrane fraction, you can measure the current
that flows through them, given certain conditions. This current is on
the order of picoamps. (For reference, electronics typically use 10-20 A
–– thirteen orders of magnitude greater.)
- The trace you see after
measuring the current reveals that individual channels open and
close very quickly and apparently randomly. By varying the voltage
to which the channels are subjected, however, one can vary the
length of time those channels will remain open (or closed).
- To keep everything straight:
- Equilibrium potential: applies to specific ions
- Resting membrane potential: describes the
overall potential of the membrane, based on the contributions of each
ion’s weighted equilibrium potential
- Action potential: rapid and invariant change in
membrane potential, to be described next.
III – Action Potentials
- So far we have talked about static situations ––
resting membrane potentials. How do you change this potential to create
an electrical signal?
- The cell uses action potentials, which are rapid,
transient, and invariant changes in Vm. The whole process
takes 2-3 ms.
- What does invariant refer to?
- The shape, size, and duration of an action
potential is always the same, for reasons to be explained next time.
The only variable aspect is the frequency at which they occur.
- If action potentials are always the same, how can
you encode anything?
- Frequency: different frequencies indicate
different stimulus intensities, quantities. A typical firing
frequency is between 4-40 Hz, though neurons can fire at 100 Hz or
- Pathway: connections are specific, so an
action potential down a certain neuronal tract is assumed to code
for a certain stimulus quality. That is, an electrical signal
in the optic nerve must, by definition, code for a visual stimulus.
(Or, by occurring in the optic nerve, an action potential is assumed
to be coding for visual stimulus.)
- Population frequency: Sometimes, stimulus
intensity is also coded for by the number of relevant neurons firing
action potentials at the same time.
- General terms to describe changes in membrane
- Hyperpolarization; change in voltage in the
negative direction. A cell that goes from –40 mV to –70 mV has
- Depolarization: change in voltage in the
positive direction. A cell that goes from –40 mV to –20 mV has
depolarized. So has a cell that goes from +20 to +40 mV.
- Action potential was discovered by recording from
the squid giant axon.
- Several distinct phases:
- 1) Slight, steady depolarization
- (threshold crossed)
- 2) Rapid depolarization – the “spike” in the
picture. This is called the rising phase.
- 3) Rapid hyperpolarization, the downward part
of the spike. This is called the falling phase.
- 4) Undershoot: the cell hyperpolarizes beyond
its resting membrane potential. While it is extra hyperpolarized, it
is in the refractory period and cannot fire another action potential
until it starts to move back toward normal RMP.
- How do these various phases arise?
- As expected, through changes in relative
- During depolarization, sodium channels open.
The sodium equilibrium potential of +50 is thus weighted more
heavily, and the cell’s voltage moves toward it.
- The cell enters the rising phase because
lots of sodium channels suddenly open. So the +50 value is
weighted even more heavily.
- All of a sudden, lots of potassium channels
then open. The potassium equilibrium potential is now the more
heavily weighted, so the cell races back down toward –75 mV … this
is the falling phase and undershoot.
- The cell then equilibrates the Na and K
permeabilities to normal and reaches standard RMP.
- IMPORTANT: at no point have you changed
the concentrations on either side of the membrane! Ions are
indeed moving, but these changes are negligible as far as
concentrations are concerned. All that has thus really changed
are the RELATIVE permeabilities to the various ions, and thus
which ones contribute more strongly to the cell’s membrane
- Firing an action potential, then, simply
involves changing the number of open channels permeating a