C2006/F2402 -- 2005 --Outline of Lecture
#18 – Electrical Communication #2
(c) Stuart Firestein,
New York, NY.
03/31/2005 04:46 PM
Notes by Chris Kelly
Some links to animations and additional information on neuroscience are
on the study guides for lectures 16 & 18 from 2004. See
lecture 16 & 17 and
lecture 18. If you need a back up text for the material that isn't in
Becker, you might want to try
I. Action Potential
- Brief Review
- Action potentials are invariant and rapid changes in
membrane potential used for signaling.
- Depolarization (initial)
- Stimulus causes the ligand-gated sodium channels to
open, causing a passive spread of depolarization inside the cell.
- Rising phase
- If that depolarization is sufficient (10 to 15 mV
more positive), voltage-gated sodium channels at the axon hillock suddenly
open, causing an enormous influx of sodium and the rapid depolarization
- This is essentially a positive-feedback cycle:
sodium entering the cell causes it to depolarize. These depolarized
conditions cause more sodium to enter the cell (because voltage-gated
channels open). This depolarizes the cell even more, making more sodium
channels open, and so on.
- Falling Phase
- Two factors contribute to the cell then racing back
down toward negative potential:
- 1) Voltage-gated sodium channels inactivate after
being open for a certain time. So, those channels that opened,
permitting the depolarization, slam shut and cannot be opened again
until the cell has “reset” itself back to RMP.
- 2) Voltage-gated potassium channels, which were
tripped during the depolarization (around –20 mV), begin to open. Why
did they not open as soon as the voltage hit –20 mV? They are slow to
undergo the proper conformational changes.
- The net effect is that the permeability to potassium
once again far outweighs that to sodium, so the cell approaches EK.
- The potassium permeability is so high, in fact, that
the cell goes closer to EK than during RMP – it hyperpolarizes.
This brief hyperpolarization can be divided into two phases.
- Absolute refractory period (negative slope)
- Voltage-gated sodium channels are still
inactivated, and thus cannot be opened by anything. Since action
potentials depend on these channels, no action potential is possible.
Also, even if such an Na influx were possible, the K current is too
high to be overcome.
- Relative refractory period (positive slope)
- Voltage-gated sodium channels begin to be
released from inactivation, making action potential possible again,
though more stimulus than usual is required since the cell is farther
from threshold than usual.
- Recall that there are no appreciable changes in
concentration at any point in this action potential. All that has changed are
the relative permeabilties of potassium and sodium.
- In fact, were you to poison the Na/K pump, eliminating
the cell’s ability to restore those ions to the correct side of the
membrane, the neuron could still fire another 150,000 action potentials
before the concentrations started to become insufficient.
- Notice that there is little room for variety in this
process, which is why action potentials are (1) invariant, and (2)
all-or-nothing. You cannot have half of an action potential.
To review the action potential, try problem 8-2,
A-C, & 8-3 to 8-4.
- So what is the use of all this? An action potential
is worthless if it does not travel somewhere.
- Action potentials are designed for long-distance
signaling, unlike graded changes in potential (i.e. depolarizations that do
not reach threshold and do vary in amplitude, unlike action potentials).
- The action potential is propagated along the axon.
- Think of the axon like a fuse: when you light a
fuse, the end heats up the next segment, which flares up and heats up the
following segment, which then flares up. Unlike a piece of string, a fuse
carries the flame all the way down to the other end.
- Where does the action potential begin?
- At the beginning of the axon, where it first leaves
the soma, there is a concentration of voltage-gated sodium channels. This
area is called the initial segment, or axon hillock. The propagation down
the axon begins with these channels opening.
- When these channels open, positive charge enters the
cell and spreads passively down the axon. This positive charge trips the
next voltage-gated sodium channels on the axon, causing a sodium influx
there, which then causes the next channels to open, and so on.
- Why doesn’t the signal go backward?
- Remember the absolute refractory period. The positive
charge will, in fact, passively spread in both directions in the axon. When
it reaches the segment that just fired, however, those voltage-gated sodium
channels will still be inactivated, and thus unable to fire an AP.
- How can one ensure that the propagation will make it?
- Axons can be leaky, and concentration of voltage-gated
sodium channels can vary. A situation could arise in which the positive
charge that enters the axon is not able to trip the next channel in the
series. This is overcome in two ways.
- In invertebrates, the axons are wider, and thus the
conductance is greater. So charge is more easily able to spread, and
propagation is ensured.
- In vertebrates, many axons are myelinated.
Myelin is a fatty substance produced by glial cells that can wrap itself
around the axon membrane. This produces an insulating effect, allowing
charge to travel more easily in the axon.
- In the first case, you have reduced the cable
resistance. In the second case, you have increased the membrane resistance
(and thus reduced “leakiness”). Both result in more conductance down the
- The myelin “sheath” is useless, however, unless it
- Ions clearly cannot pass through myelin. So having a
myelin sheath around the axon would prevent signaling unless there
are gaps in the myelin dotted along the axon. These are known as the nodes
- At each node, there is a high concentration of
sodium and potassium channels. So when the positive charge reaches the
node, the series of electrical events described by the action potential
will occur there. The signal is regenerated. This kind of signaling is
called saltatory conduction, since it appears the action potential is
“jumping” from one node to the next.
- Since action potentials take some time, having the
myelin sheath accelerates the signaling process by reducing the number of
action potential events along the axon. So signaling in myelinated axons
is faster than in unmyelinated axons.
- Conduction velocity can be up to 10 m/s.
- There are several demyelinating diseases in the
nervous system. Multiple sclerosis (MS) is a famous one, in which an
inappropriate autoimmune response results in the destruction of myelin,
thereby interrupting signaling in nerves. One can see these diseases in
images of the nervous system because the characteristic white color of the
myelin is missing in certain places.
- Note on terminology: even though the cell is firing
action potentials all along its axon, we say that it has fired a single
action potential and simply propagated it.
To review propagation, try problem 8-2 D-E & 8-6.
- So the action potential travels down the axon –– what
- The end of the axon is a specialized area with
characteristic proteins and biochemical processes. It is essentially
independent from the soma, even though it gets its material from there.
- This terminal area links one neuron to another,
enabling intercellular communication. These areas of contact are called
synapses, and you have about 1014 of them in your brain –– three
orders of magnitude more than neurons.
- What is the nature of the synapse?
- The big question is whether the link is an electrical
or chemical one.
- Otto Loewi showed that these links are primarily
chemical by placing two frog hearts in bath solution, innervating only one
of them, and then observing that both hearts are affected. In that
particular case, the chemical was acetylcholine, and it was causing the
hearts to slow down their beating. There was no electrical connection
between the hearts, just a chemical one (the solution in which they were
- There are some electrical synapses in the body;
they are created by gap junctions. The myocytes in the heart, for example,
are connected by electrical synapses so that they can depolarize as a unit,
giving a unified heartbeat.
- What is the structure of the synapse?
- The presynaptic neuron is that which fired the action
potential along its axon, to the axonal terminal. The postsynaptic neuron is
the one that its axon contacts.
- There is a space between the two cells known as the
synaptic cleft. It is typically very narrow –– 20 to 40 nm –– but a definite
- The major players:
- Presynaptic side: calcium and vesicles full of
- Postsynaptic side: neurotransmitter receptors
- The process:
- The action potential races down the axon and
depolarizes the terminal. This causes voltage-gated Ca++
channels at the terminal to open. Since the calcium concentration is 5 mM
outside the cell and 0.1 µM inside, calcium rushes in. (FYI: lots of
calcium inside the cell is a bad thing. So that’s why the concentrations
are the way they are.)
- Calcium influx causes the vesicles full of
neurotransmitter to dock with the presynaptic membrane and then fuse with
it, causing exocytosis of neurotransmitter into the synaptic cleft.
- The NT’s diffuse cross the synaptic cleft and
contact receptors on the postsynaptic side.
- What are the kinds of neurotransmitters?
- Many are amino acids: glutamate, GABA (g-amino
butyric acid), glycine are examples.
- There are also amino acid derivatives: serotonin,
dopamine, epinephrine, etc.
- Acetylcholine (ACh) is another.
- What are their overall effects?
- Neurotransmitters are considered excitatory or
inhibitory, based on whether they produce a depolarization or
hyperpolarization (respectively) in the postsynaptic neuron.
- Glutamate is the main excitatory NT in the CNS;
glycine and GABA are the main inhibitory ones in the CNS. ACh is the primary
NT in the PNS.
- How are these electrical effects produced?
- When NT’s cross the cleft, they bind to receptors.
These receptors are of two kinds:
- Ionotropic: these receptors are also ion channels.
When ligand binds, conformational changes in the channel subunits are
induced, resulting in the opening or closing of the pore. This is a
one-to-one effect: the ligand affects only one channel.
- Metabotropic: the receptors are coupled to
G-Proteins, and the cascade is initiated by the binding of ligand. The
produced cascade usually results in the opening/closing of channels via
second messangers. One ligand can thus affect many channels in this case.
- In both cases, the opening of channels causes the flow
of ions, which has an electrical effect.
- If the net electrical effect is a hyperpolarization,
than the NT has produced an IPSP (inhibitory post-synaptic potential).
Depolarization -> EPSP (excitatory …).
- Note that there is such a thing as a gaseous
- Nitric oxide, NO, is one example. Unlike solid
neurotransmitters, these can freely diffuse from one cell to another.
- NO initiates a cascade that results in guanalyl
cyclase (GC) producing cGMP, whose net effect is vasodilation in many cases.
Viagra inhibits PDE-3 from breaking down cGMP, thereby maintaining
vasodilation and, hence, an erection.
- GC and cGMP are analogous to AC and cAMP, which we
have already studied. The essential difference is just the nucleotide
To review synapses etc., try problems 8-8 A-G &
8-9. (8-10 & 8-11 are also about synapses.)