C2006/F2402 -- 2005 --Outline of Lecture
#17 – Electrical Communication #1
(c) Stuart Firestein,
New York, NY.
03/30/2005 05:07 PM
Notes by Chris Kelly
1. Neurons: structure and
- 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 phase.
- The main function: information transfer and signaling
- 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
- You step on a thumbtack, a pain signal goes to the
spinal cord, contacts a motorneuron, signal goes out to the leg muscle,
- Two major divisions: central nervous system (CNS)
and peripheral nervous system (PNS).
- CNS: brain and spinal cord.
- PNS: everything else (motoneurons, sensory neurons).
- There are a few exceptions: the retina, for example,
is in the back of the eye but is considered part of the CNS.
- The functional unit is a neuron.
- There are 1011 neurons in the adult human
- 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 time).
- 2) Specific connectivity: the specificity of the
connections in the nervous system is critical. Think of the wires behind
- 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,
- 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, muscle, etc.
- We can now revisit the dynamic polarization principal
- 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 potential.
- 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 at ground.
- 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
- A typical distribution is:
- Other ions involved
- Inside: negatively-charged proteins, chloride
- 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 membrane.
- 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=
- 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 are obtained with the Nernst
equation. See your textbook if you are interested.
- 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
- 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
- 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 cell.
- 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
- 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
- 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
- The cell uses action potentials, which are rapid,
transient, and invariant changes in Vm. The whole process takes
- 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
- 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 faster.
- 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
- 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
- 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! All that has changed are
the RELATIVE permeabilities to the various ions, and thus which ones
contribute more strongly to the cell’s membrane potential.
- Firing an action potential, then, simply involves
changing the number of open channels permeating a particular ion.